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Am J Physiol Heart Circ Physiol 287: H40-H45, 2004. First published February 19, 2004; doi:10.1152/ajpheart.01179.2003
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Gender differences in myogenic tone in superoxide dismutase knockout mouse: animal model of oxidative stress

Sukrutha Veerareddy,1,2 Christy-Lynn M. Cooke,1 Philip N. Baker,2 and Sandra T. Davidge1

1Perinatal Research Centre, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; and 2Maternal and Fetal Health Research Centre, University of Manchester, Manchester M13 0JH, United Kingdom

Submitted 15 December 2003 ; accepted in final form 12 February 2004


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Oxidative stress mediated by prooxidants has been implicated in the pathogenesis of vascular disorders. However, the effect of prooxidants on myogenic regulation of vascular function and the differential influence of gender is not known. SOD, an intracellular enzyme, restricts excess prooxidant levels and may limit vascular dysfunction. We therefore tested the effects of Cu,Zn SOD deficiency on vascular tone in both male and female SOD knockout (SOD–/–) mice. We hypothesized that myogenic tone would be enhanced in SOD–/– mice by excess prooxidants compared with wild-type control mice. Indeed, resistance-sized mesenteric arteries from SOD–/– mice exhibited enhanced myogenic tone compared with control mice. Myogenic tone was lower in female than male control mice. Interestingly, this gender effect was absent in SOD–/– mice, such that myogenic tone of mesenteric arteries from females was equated to that of arteries from males. Furthermore, the pathways that modulate myogenic tone were diverse. In both male and female control mice, inhibition of prostaglandin H synthase (PGHS) and nitric oxide synthase (NOS) pathways enhanced myogenic tone. In female SOD–/– mice, inhibition of PGHS and NOS pathways enhanced myogenic tone to a greater extent compared with control mice. Conversely, in male SOD–/– mice, NOS and PGHS inhibition did not alter tone and only inhibition of gap junctions enhanced myogenic tone. In conclusion, this study revealed enhanced myogenic tone in SOD–/– mice compared with control mice. Furthermore, Cu,Zn SOD deficiency particularly enhanced myogenic tone in female mice such that their vascular tone attained the level of male SOD–/– mice, possibly mediated by prooxidants.

vascular tone; genetic mouse model; sex

OXIDATIVE STRESS MEDIATED by prooxidants has been implicated in the pathogenesis of various vascular disorders including atherosclerosis, hypertension, aging, diabetes mellitus, and preeclampsia that are associated with endothelial dysfunction (7, 9, 20). Numerous studies in humans (3) and animals (6, 9) suggest that increased superoxide production contributes significantly to the functional alterations of arteries. Superoxide anion has the ability to inactivate the potent vasodilator nitric oxide (NO) to form peroxynitrite and cause an impairment of endothelium-dependent vasorelaxation (6, 24, 36). Potential sources of vascular superoxide production include NAD(P)H-dependent oxidases (26), xanthine oxidase (38), lipoxygenase, and endothelial NO synthases (eNOS) (32). eNOS, in addition to producing NO, a potent vasodilator, under certain conditions may be a source of superoxide production (16) because of enzymatic "uncoupling" and lead to an imbalance between levels of NO and superoxide seen in vascular diseases. SODs are endogenous antioxidant enzymes that limit increases in superoxide levels and therefore play an important role in defense against oxidative stress. Therefore, in states of SOD deficiency, enhanced levels of superoxide may have profound effects on vascular tone by reducing the vasodilator actions of NO in addition to producing the oxidative peroxynitrite radical.

We used a mouse model that is selectively deficient in Cu,Zn SOD to test the vascular consequences of oxidative stress because derangement of SOD system and related prooxidant molecules exists in various pathologies (30, 34, 39). A recent study suggests that selective deficiency of Cu,Zn SOD in this animal model leads to decreased SOD protein and activity and a consequent elevation of prooxidant superoxide in nonvascular and vascular tissues and associated vascular dysfunction in carotid and cerebral arterioles (6). Similarly, enhanced peroxynitrite formation was recently demonstrated in vascular tissues in the SOD knockout (SOD–/–) mouse in our laboratory (5). However, in this animal model of oxidative stress, myogenic tone has not been evaluated.

Myogenic tone is the ability of microvessels to alter their tone in response to changes in intraluminal pressure and is of critical importance for regulation of blood flow to various tissues (8). Although the precise mechanism is unclear, and likely to be very complex, myogenic tone exerts direct effects on smooth muscle and results in depolarization and increased intracellular Ca2+. It is widely accepted that the vascular tone is modulated by the generation of endothelium-derived vasodilators such as NO and prostacyclin and NO/prostanoid-independent relaxations that involve direct heterocellular signaling between endothelial and smooth muscle cells via gap junctions (12).

Recent studies have indicated that the nature of myogenic activation in resistance vessels can be radically altered by the development of pathological conditions including hypertension and diabetes mellitus (7, 9, 21), conditions that are associated with oxidative stress. Therefore, we studied myogenic tone in this animal model of SOD deficiency to enhance the knowledge of oxidative stress-mediated vascular dysfunction and also to evaluate whether there are gender differences in modulation of myogenic tone. We hypothesized that resistance-sized blood vessels from SOD–/– mice will have enhanced myogenic tone that may differentially affect tone in both sexes as a result of alteration of PGHS, NOS, and NO/prostanoid-independent mechanisms.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Heterozygous pairs of B6;129S-SOD1 mice purchased from Jackson Laboratories (Bar Harbor, ME) were housed in an virus antigen-free (VAF), temperature- and humidity-controlled environment and fed standard lab chow and water ad libitum. Two groups of mice (aged 5–7 mo) were used for vascular studies: homozygous Cu,Zn SOD-deficient (Cu,Zn SOD–/–) mice and wild-type control mice. Mice were bred in a VAF environment and genotyped at the University of Alberta Transgenic Facility. This study was approved by the University of Alberta Health Sciences Animal Policy and Welfare Committee and was in accordance with the Canadian Council on Animal Care.

After death (cervical dislocation), mesentery was removed and placed immediately in freshly prepared cold Dulbecco's medium (23). Dulbecco's medium was prepared with Dulbecco's modified Eagle's medium base (Sigma) supplemented with (in mM) 1 sodium pyruvate, 25 sodium bicarbonate, 5 HEPES, and 5 glucose. We chose the mesenteric bed because it contributes substantially to vascular resistance (4). Second-order mesenteric arteries were dissected of surrounding fat and mounted on a pressure myograph as previously described (Living Systems Instrumentation, Burlington, VT; Ref. 15). Dulbecco's medium was maintained at 37°C and pH 7.4. The vessels were imaged with a video camera, and internal diameter and wall thickness were measured with a video dimension analyzer.

Experimental Protocols: Assessment of Myogenic Tone

After being mounted, blood vessels were equilibrated for 30 min at an intraluminal pressure of 50 mmHg and prestretched by increasing intraluminal pressure from 50 to 75 mmHg and then returning it to 50 mmHg immediately. The vessels were then allowed to equilibrate at 50 mmHg for another 30 min.

After the equilibration process, the intraluminal pressure was reduced to 10 mmHg and the vessels were further stabilized for 10 min. The pressure was then increased from 10 to 100 mmHg in 10-mmHg increments. A diameter measurement was taken 5–6 min after each pressure step.

This protocol for assessing myogenic tone was then repeated in the presence of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 100 µM) and the PGHS inhibitor meclofenamate (1.0 µM) after incubation for 20 min. The involvement of gap junctions was determined by incubation with the gap junction inhibitor 18{alpha}-glycyrrhetinic acid (18{alpha}-GA, 100 µM) for 30 min. At the conclusion of each experiment passive curves were constructed in the absence of extracellular Ca2+. Time-control experiments were performed to ascertain the repeatability of vessel responses in wild-type and SOD–/– mice.

Calculations

Calculations were performed with the following formula to calculate percent myogenic tone at each pressure step: % myogenic tone = (D1 – D2)/D1 x 100, where D1 is the internal diameter in Ca2+-free medium and D2 is the internal diameter in the presence of extracellular Ca2+.

Data Analysis

Two-way repeated-measures ANOVA with post hoc Bonferroni's test for multiple comparisons was used to assess differences in constrictor responses at each pressure step above 60 mmHg between groups of arteries because myogenic tone was evident >60 mmHg. Kruskal-Wallis one-way ANOVA on ranks was used to assess differences in arterial diameters. Data are expressed as means ± SE. Statistical significance was accepted at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Effect of Intraluminal Pressure on Vessel Reactivity in Wild-Type and SOD–/– Mice

Myogenic tone in mesenteric arteries from SOD–/– mice was enhanced compared with those from wild-type control mice (Fig. 1A; P = 0.029). Figure 1B illustrates a comparison of myogenic tone in male SOD–/– and wild-type mice. Male wild-type mice exhibited lower myogenic tone compared with male SOD–/– mice (Fig. 1B; P = 0.034). A similar trend to lower myogenicity was observed in female wild-type mice compared with female SOD–/– mice, and this effect was more dramatic compared with male mice (Fig. 1C; P < 0.001). There were no significant differences in arterial diameters (at 10 and 60 mmHg) in the four groups (Table 1).



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  		Fig. 1. A: myogenic responses in mesenteric arteries from SOD–/– mice [SOD knockout (SODKO)] vs. wild-type mice. SOD–/– mice exhibited enhanced myogenic tone as evidenced by the greater decrease in diameter for each pressure step and reached statistical significance at ≥80 mmHg (P = 0.029). B: myogenic tone is higher in mesenteric arteries from male SOD–/– mice compared with male wild-type mice (P = 0.034). C: a similar trend of enhanced myogenic tone was observed in mesenteric arteries in female SOD–/– mice compared with wild-type mice (P < 0.001).

 

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  		Table 1. Comparison of diameters in small mesenteric arteries from wild-type and SOD–/– mice

 
Effect of NOS, PGHS, and Gap Junction Inhibition on Myogenic Tone

Male mice.
WILD TYPE. In mesenteric arteries from male wild-type mice, incubation with meclofenamate or L-NAME enhanced tone, suggesting a role for PGHS and NOS, respectively, in the modulation of myogenic tone (Fig. 2, A and B, P = 0.002 and P = 0.042, respectively). However, gap junction inhibition had no additional effect on myogenic tone when used in combination with inhibitors of PGHS and NOS (Fig. 2C, P = 0.076).



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  		Fig. 2. Male wild-type mice. A: effect of meclofenamate [prostaglandin H synthase (PGHS) inhibitor] and NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide synthase (NOS) inhibitor] on myogenic tone in mesenteric arteries from male wild-type mice. A and B: myogenic tone was enhanced in the presence of meclofenamate (A) and L-NAME (B) in mesenteric arteries from male wild-type mice (P < 0.05 for meclofenamate and L-NAME vs. control). C: gap junction inhibitor 18{alpha}-glycyrrhetinic acid (18{alpha}-GA) did not appear to modulate myogenic tone more than NOS and PGHS inhibitors.

 

SOD–/–. Conversely, in arteries from the male SOD–/– mice, meclofenamate and L-NAME treatment did not augment myogenic tone (Fig. 3, A and B, P = 0.181 and P = 0.958, respectively), but gap junction inhibition with 18{alpha}-GA significantly enhanced myogenic tone, suggesting a role for non-NO, non-prostacyclin pathways in modulation of vascular tone in states of excess prooxidant environment (Fig. 3C, P = 0.005).



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  		Fig. 3. Male SOD–/– mice. Effect of meclofenamate (PGHS inhibitor) and L-NAME (NOS inhibitor) on myogenic tone in mesenteric arteries from male SOD–/– mice is shown. A and B: myogenic tone was unaltered by meclofenamate (A) and L-NAME (B) in mesenteric arteries from male SOD–/– mice. C: myogenic tone was enhanced in the presence of the gap junction inhibitor 18{alpha}-GA (P = 0.005).

 
Female mice.
WILD TYPE. Similar to males, in female wild-type mice, inhibition of PGHS and NOS pathways led to significant enhancement of myogenic tone (Fig. 4, A and B, P = 0.045 and P = 0.023, respectively). In addition, inhibition of gap junctions was without effect on myogenic tone, comparable to the effect observed in male wild-type mice (Fig. 4C, P = 0.098).



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  		Fig. 4. Female wild-type mice. Effect of meclofenamate (PGHS inhibitor) and L-NAME (NOS inhibitor) on myogenic tone in mesenteric arteries from female wild-type mice is shown. A and B: myogenic tone was enhanced in the presence of meclofenamate (A) and L-NAME (B) in mesenteric arteries from female wild-type mice (P < 0.05 for meclofenamate and L-NAME vs. control). C: gap junction inhibitor did not appear to modulate myogenic tone more than NOS and PGHS inhibitors.

 

SOD–/–. However, in contrast to male SOD–/– mice, in the female SOD–/– mice, inhibition of PGHS and NOS led to greater enhancement of myogenic tone (Fig. 5, A and B, P = 0.015 and P = 0.002, respectively). Gap junction inhibition enhanced myogenic tone only in the male SOD–/– mice and did not alter myogenic tone in the female SOD–/– mice (Fig. 5C, P = 0.208).



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  		Fig. 5. Female SOD–/– mice. Effect of meclofenamate (PGHS inhibitor) and L-NAME (NOS inhibitor) on myogenic tone in mesenteric arteries from female SOD–/– mice is shown. A and B: myogenic tone was enhanced in the presence of meclofenamate (A) and L-NAME (B) in mesenteric arteries from female SOD–/– mice (P < 0.05 for meclofenamate and L-NAME vs. control). C: gap junction inhibitor did not appear to modulate myogenic tone more than NOS and PGHS inhibitors.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Various studies have indicated that oxidant stress plays a causative role in several pathological conditions such as aging, hypertension, diabetes mellitus, and preeclampsia (30, 34, 39). The purpose of this study was twofold: first, to ascertain whether myogenic tone is altered in a model of oxidative stress, and, second, to determine whether there were any gender differences in the modulation of myogenic tone in this animal model.

Resistance-sized mesenteric arteries from SOD–/– mice exhibited greater myogenic tone compared with those from control wild-type mice, suggesting that enhanced prooxidants alter vascular tone. In accord with the findings of our study, enhanced myogenic tone was noted in animal models of obesity and hyperlipidemia (9, 27). Although evolving evidence suggests that myogenic tone is enhanced in the presence of oxidative stress, mechanism(s) that are involved in influencing vascular tone are not fully defined. Data suggest that prooxidants may alter vascular tone by blocking hyperpolarization (2). Additionally, elevation of transmural pressure can release prooxidant superoxide from vascular tissues (13, 14, 31), impair vasodilation (19), and also enhance production of peroxynitrite with consequent vascular dysfunction. Additional vascular data from our laboratory (5) and others (6) using the SOD–/– mouse model have demonstrated elevated superoxide and peroxynitrite production in the vascular tissues and altered responses to vasoactive agents in small and large arteries. Therefore, it is evident that SOD deficiency can lead to overall alteration of vascular reactivity including myogenic tone due to enhanced oxidative stress.

Experimental evidence in young animals, including our own data, suggests that myogenic tone is lower in females compared with males (10, 18, 22, 37). The myogenic tone that was noted in the female wild-type mice was considerably lower than in female C57BL/6J mice from our previous study (33). These differences of vascular function among mouse strains were reported previously (28). Nonetheless, in our animal model of SOD deficiency, perhaps due to an enhanced prooxidant environment, myogenic tone was enhanced to a greater extent in the females such that the tone became equivalent to the males—an effect similar to that associated with states of oxidative stress such as menopause and aging. As well, altered vascular reactivity could have implications for perfusion of various key organs in the body (6). Indeed, female SOD–/– mice in our study failed to become pregnant, similar to those in other studies (17). However, we did not examine the causes of infertility in the current study.

In the wild-type control group, female mice exhibited significantly lower myogenic tone compared with male mice. Myogenic tone was modulated to a similar extent by both PGHS and NOS pathways in both male and female mice without any additional effect on tone from gap junction-mediated mechanisms.

However, in addition to the greater enhancement of myogenicity in the female SOD–/– mice, we also observed gender differences in the modulation of myogenic tone. Inhibition of PGHS and NOS pathways enhanced myogenic tone only in the female SOD–/– mice to a greater extent compared with the control mice, suggesting that these pathways play an important role in controlling myogenic tone. The enhanced PGHS and NOS modulation noted in the female SOD–/– mice may have been an attempt to compensate for the excess prooxidant environment. In females, estrogen is known to modulate myogenic reactivity through both endothelium-derived PGHS- and NOS-dependent mechanisms (11, 37). It is possible that the lack of gender protection in the female SOD–/– mice may be due to enhanced production of superoxide anions mediated by eNOS (30, 25) in this model. In contrast, in male SOD–/– mice, inhibition of NOS and PGHS pathways did not alter myogenic reactivity. However, inhibition of gap junctions enhanced myogenic tone similar to the other studies in which a non-NO/non-prostacyclin-mediated vasodilation ensued as a compensatory mechanism in an attempt to normalize vascular tone (1, 29, 35).

In summary, results from our study in this genetic murine model suggest that enhanced prooxidants alter myogenic reactivity compared with control mice. Furthermore, myogenic tone was enhanced to a greater extent in the arteries from female SOD–/– mice, such that the tone reached the level of vessels from male mice; this effect is similar to that which occurs in aging. The alterations of myogenic tone also seem to depend on the different mechanisms in the male and the female. Therefore, our data further contribute to the understanding of sexual dimorphism in artery function, and this animal model provides vital information regarding the effects of prooxidants on vascular tone that is important in understanding pathologies associated with oxidative stress such as aging and menopause.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This project is supported by the Canadian Institute of Health Research (CIHR). S. T. Davidge is a Canada Research Chair in Women's Cardiovascular Health and a Senior Scholar of the Alberta Heritage Foundation for Medical Research (AHFMR). S. Veerareddy is funded by the Department of Obstetrics and Gynaecology, University of Alberta, through a Wyeth-Ayerst Fellowship Award and the University of Alberta Perinatal Research Centre. C. M. Cooke is supported by a graduate studentship from CIHR and AHFMR. P. N. Baker is supported by Tommys: the baby charity.


   FOOTNOTES
 

Address for reprint requests and other correspondence: S. T. Davidge, Perinatal Research Centre, 232 HMRC, Depts. of Ob/Gyn and Physiology, Univ. of Alberta, Edmonton, Alberta, Canada T6G 2S2 (E-mail: sandra.davidge{at}ualberta.ca).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Brandes RP, Schmitz-Winnenthal FH, Feletou M, Godecke A, Huang PL, Vanhoutte PM, Fleming I, and Busse R. An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice. Proc Natl Acad Sci USA 97: 9747–9752, 2000.[Abstract/Free Full Text]
  2. Brzezinska Ak Gebremedhin D, Chilian WM, Kalyanaraman B, and Elliott SJ. Peroxynitrite reversibly inhibits Ca2+-activated K+ channels in rat cerebral artery smooth muscle cells. Am J Physiol Heart Circ Physiol 278: H1883–H1890, 2000.[Abstract/Free Full Text]
  3. Cardillo C, Kilcoyne CM, Quyyumi AA, Cannon RO 3rd, and Panza JA. Selective defect in nitric oxide synthesis may explain the impaired endothelium-dependent vasodilation in patients with essential hypertension. Circulation 97: 851–856, 1998.[Abstract/Free Full Text]
  4. Christensen KL and Mulvany MJ. Mesenteric arcade arteries contribute substantially to vascular resistance in conscious rats. J Vasc Res 30: 73–79, 1993.[ISI][Medline]
  5. Cooke CL and Davidge ST. Endothelial-dependent vasodilation is reduced in mesenteric arteries from superoxide dismutase knockout mice. Cardiovasc Res 60: 635–642, 2003.
  6. Didion SP, Ryan MJ, Didion LA, Fegan PE, Sigmund CD, and Faraci FM. Increased superoxide and vascular dysfunction in CuZnSOD-deficient mice. Circ Res 91: 938–944, 2002.[Abstract/Free Full Text]
  7. Falcone JC, Granger HJ, and Meininger GA. Enhanced myogenic activation in skeletal muscle arterioles from spontaneously hypertensive rats. Am J Physiol Heart Circ Physiol 265: H1847–H1855, 1993.[Abstract/Free Full Text]
  8. Folkow B. Myogenic mechanisms in the control of systemic resistance. Introduction and historical background. J Hypertens Suppl 7: S1–S4, 1989.[CrossRef][Medline]
  9. Frisbee JC, Maier KG, and Stepp DW. Oxidant stress-induced increase in myogenic activation of skeletal muscle resistance arteries in obese Zucker rats. Am J Physiol Heart Circ Physiol 283: H2160–H2168, 2002.[Abstract/Free Full Text]
  10. Geary GG, Krause DN, and Duckles SP. Estrogen reduces myogenic tone through a nitric oxide-dependent mechanism in rat cerebral arteries. Am J Physiol Heart Circ Physiol 275: H292–H300, 1998.[Abstract/Free Full Text]
  11. Geary GG, Krause DN, and Duckles SP. Estrogen reduces mouse cerebral artery tone through endothelial NOS- and cyclooxygenase-dependent mechanisms. Am J Physiol Heart Circ Physiol 279: H511–H519, 2000.[Abstract/Free Full Text]
  12. Griffith TM. Endothelial control of vascular tone by nitric oxide and gap junctions: a haemodynamic perspective. Biorheology 39: 307–318, 2002.[ISI][Medline]
  13. Guzik TJ, Mussa S, Gastaldi D, Sadowski J, Ratnatunga C, Pillai R, and Channon KM. Mechanisms of increased vascular superoxide production in human diabetes mellitus: role of NAD(P)H oxidase and endothelial nitric oxide synthase. Circulation 105: 1656–1662, 2002.[Abstract/Free Full Text]
  14. Guzik TJ, West NEJ, Black E, Mcdonald D, Ratnatunga C, Pillai R, and Channon KM. Vascular superoxide production by NAD(P)H oxidase: association with endothelial dysfunction and clinical risk factors. Circ Res 86: E85–E90, 2000.[ISI][Medline]
  15. Halpern W, Osol G, and Coy GS. Mechanical behavior of pressurized in vitro prearteriolar vessels determined with a video system. Ann Biomed Eng 12: 463–479, 1984.[CrossRef][ISI][Medline]
  16. Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, Skatchkov M, Thaiss F, Stahl RA, Warnholtz A, Meinertz T, Griendling K, Harrison DG, Forstermann U, and Munzel T. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res 88: E14–E22, 2001.[ISI][Medline]
  17. Ho YS, Gargano M, Cao J, Bronson RT, Heimler I, and Hutz RJ. Reduced fertility in female mice lacking copper-zinc superoxide dismutase. J Biol Chem 273: 7765–7769, 1998.[Abstract/Free Full Text]
  18. Huang A, Sun D, Kaley G, and Koller A. Estrogen maintains nitric oxide synthesis in arterioles of female hypertensive rats. Hypertension 29: 1351–1356, 1997.[Abstract/Free Full Text]
  19. Huang A, Sun D, Kaley G, and Koller A. Superoxide released to high intra-arteriolar pressure reduces nitric oxide-mediated shear stress- and agonist-induced dilations. Circ Res 83: 960–965, 1998.[Abstract/Free Full Text]
  20. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med 222: 222–235, 1999.[Abstract/Free Full Text]
  21. Izzard AS and Heagerty AM. Hypertension and the vasculature: arterioles and the myogenic response. J Hypertens 13: 1–4, 1995.[ISI][Medline]
  22. Knot HJ, Lounsbury KM, Brayden JE, and Nelson MT. Gender differences in coronary artery diameter reflect changes in both endothelial Ca2+ and ecNOS activity. Am J Physiol Heart Circ Physiol 276: H961–H969, 1999.[Abstract/Free Full Text]
  23. Loutzenhiser R, Bidani A, and Chilton L. Renal myogenic response: kinetic attributes and physiological role. Circ Res 90: 1316–1324, 2002.[Abstract/Free Full Text]
  24. Lynch SM, Frei B, Morrow JD, Roberts LJ II, Xu A, Jackson T, Reyna R, Klevay LM, Vita JA, and Keaney JF Jr. Vascular superoxide dismutase deficiency impairs endothelial vasodilator function through direct inactivation of nitric oxide and increased lipid peroxidation. Arterioscler Thromb Vasc Biol 17: 2975–2981, 1997.[Abstract/Free Full Text]
  25. Matoba T, Shimokawa H, Nakashima M, Hirakawa Y, Mukai Y, Hirano K, Kanaide H, and Takeshita A. Hydrogen peroxide is an endothelium-derived hyperpolarizing factor in mice. J Clin Invest 106: 1521–1530, 2000.[ISI][Medline]
  26. Rajagopalan S, Kurz S, Munzel T, Tarpey M, Freeman BA, Griendling KK, and Harrison DG. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 97: 1916–1923, 1996.[ISI][Medline]
  27. Ramirez RJJ, Novak J, Johnston TP, Gandley RE, Mclaughlin MK, and Hubel CA. Endothelial function and myogenic reactivity in small mesenteric arteries of hyperlipidemic pregnant rats. Am J Physiol Regul Integr Comp Physiol 281: R1330–R1337, 2001.[Abstract/Free Full Text]
  28. Ryan MJ, Didion SP, Davis DR, Faraci FM, and Sigmund CD. Endothelial dysfunction and blood pressure variability in selected inbred mouse strains. Arterioscler Thromb Vasc Biol 22: 42–48, 2002.[Abstract/Free Full Text]
  29. Scotland RS, Chauhan S, Vallance PJT, and Ahluwalia A. An endothelium-derived hyperpolarizing factor-like factor moderates myogenic constriction of mesenteric resistance arteries in the absence of endothelial nitric oxide synthase-derived nitric oxide. Hypertension 38: 833–839, 2001.[Abstract/Free Full Text]
  30. Touyz RM. Oxidative stress and vascular damage in hypertension. Curr Hypertens Rep 2: 98–105, 2000.[Medline]
  31. Ungvari Z, Csiszar A, Huang A, Kaminski PM, Wolin MS, and Koller A. High pressure induces superoxide production in isolated arteries via protein kinase C-dependent activation of NAD(P)H oxidase. Circulation 108: 1253–1258, 2003.[Abstract/Free Full Text]
  32. Vasquez-Vivar J, Kalyanaraman B, Martasek P, Hogg N, Masters BS, Karoui H, Tordo P, and Pritchard KA Jr. Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci USA 95: 9220–9225, 1998.[Abstract/Free Full Text]
  33. Veerareddy S, Cooke CL, Baker PN, and Davidge ST. Vascular adaptations to pregnancy in mice: effects on myogenic tone. Am J Physiol Heart Circ Physiol 283: H2226–H2233, 2002.[Abstract/Free Full Text]
  34. Venarucci D, Venarucci V, Vallese A, Battila L, Casado A, De La Torre R, and Lopez Fernandez ME. Free radicals: important cause of pathologies refer to ageing. Panminerva Med 41: 335–339, 1999.[ISI][Medline]
  35. Waldron GJ, Ding H, Lovren F, Kubes P, and Triggle CR. Acetylcholine-induced relaxation of peripheral arteries isolated from mice lacking endothelial nitric oxide synthase. Br J Pharmacol 128: 653–658, 1999.[CrossRef][ISI][Medline]
  36. Wei EP, Kontos HA, Christman CW, Dewitt DS, and Povlishock JT. Superoxide generation and reversal of acetylcholine-induced cerebral arteriolar dilation after acute hypertension. Circ Res 57: 781–787, 1985.[Abstract/Free Full Text]
  37. Wellman GC, Bonev AD, Nelson MT, and Brayden JE. Gender differences in coronary artery diameter involve estrogen, nitric oxide, and Ca2+-dependent K+ channels. Circ Res 79: 1024–1030, 1996.[Abstract/Free Full Text]
  38. White CR, Darley-Usmar V, Berrington WR, Mcadams M, Gore JZ, Thompson JA, Parks DA, Tarpey MM, and Freeman BA. Circulating plasma xanthine oxidase contributes to vascular dysfunction in hypercholesterolemic rabbits. Proc Natl Acad Sci USA 93: 8745–8749, 1996.[Abstract/Free Full Text]
  39. Wiktor H and Kankofer M. Superoxide dismutase activity in normal and preeclamptic placentas. Ginekol Pol 69: 915–918, 1998.[Medline]



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