INTRODUCTION

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PARTIAL AORTIC CONSTRICTION proximal to the renal arteries elicited a prompt and sustained (45-min) rise in carotid pressure associated with a stable reflex bradycardia in conscious intact rats (16, 17). This rise in arterial pressure has been attributed to the sudden increase in impedance to aortic flow and associated neurohumoral responses involving, particularly, angiotensin (16, 23) and vasopressin (5, 15, 17), whereas the stable reflex bradycardia is mediated mainly through vagal activation (8, 19, 20).

The model of abdominal aortic coarctation hypertension is somewhat similar to one-kidney, one-clip hypertension, since in both models the kidneys are under low perfusion pressure. In the latter model a sympathoexcitatory vasoconstrictor reflex (renal pressor reflex) has been shown to be triggered (2-4), suggesting that a similar reflex could be triggered by aortic coarctation. Moreover, there is a body of evidence indicating that the sympathetic nervous system, via the renal nerves, plays an important role in the pathogenesis of renovascular hypertension in humans and laboratory animals (12, 22). However, occlusion of the descending aorta in anesthetized cats inhibits almost completely sympathetic renal nerve activity (11). In addition, conscious rats submitted to an acute (45-min) aortic coarctation hypertension exhibited a marked decrease in plasma norepinephrine concentration that was attributed to reflexly mediated inhibition of the sympathetic outflow by the sinoaortic baroreceptors (18).

The objective of the present study was to evaluate the contribution of the sympathetic nervous system to the hypertensive response to acute (45-min) aortic coarctation in conscious rats with intact baroreceptors or with sinoaortic denervation to preclude any inhibitory influence of the baroreceptors on sympathetic activity.

	METHODS

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Experiments were conducted on male Wistar rats (280-320 g) receiving standard laboratory rat chow and water. Two days before the experiment the rats were anesthetized with pentobarbital sodium (40 mg/kg ip), and after laparotomy a pneumatic cuff was implanted around the aorta immediately below the diaphragm, as described elsewhere (17, 18). The tubing connected to the cuff was exteriorized through the animal's back. On the day before the experiment the rats were anesthetized with ether and submitted to sham operation or sinoaortic deafferentation according to the technique described by Krieger (7), and polyethylene catheters were inserted into the femoral artery and left carotid artery for arterial pressure measurement. In some animals a catheter was inserted into the femoral vein for drug injection. The distal ends of the catheters were exteriorized through the animal's back, together with the tubing connected to the cuff. The experiments were conducted with the animals unrestrained in individual cages in a quiet environment. Carotid and femoral arterial pressures were measured continuously with a pressure transducer (model P23Gb, Statham, Hato Rey, PR), and the signal was recorded with a thermal recorder (model 7848, Hewlett-Packard, Palo Alto CA). Heart rate (HR) was determined by counting arterial pulses at higher recorder speed.

Experimental protocol. After basal measurement of carotid pressure and HR, the balloon inside the cuff was filled with liquid to partially constrict the aorta and thus maintain the arterial pressure distal to the cuff (mean femoral pressure) precisely at 50 mmHg for 45 min. Aortic coarctation was performed (n = 7 in each group) in intact (sham-operated) and sinoarotic-denervated (SAD) rats treated or not with guanethidine (50 mg · kg¹ · day¹ ip; Sigma Chemical, St. Louis, MO) for 5 days/wk for 5 wk (6), which destroys sympathetic neurons. Sympathectomy induced by guanethidine was verified on the day of the experiment by the abolition of the pressor response due to the release of catecholamines from the nerve endings caused by tyramine (100 µg iv) (21). In another series of experiments the acute hypotensive effect due to the selective pharmacological blockade of ₁-adrenergic receptors with prazosin (1 mg/kg iv) was examined in intact (n = 5) and SAD (n = 6) rats 10 min after the beginning of aortic coarctation; during this period the increase in arterial pressure was already established and the effect of prazosin was observed over the next 15 min.

	RESULTS

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Effect of chronic sympathectomy on the hypertensive response of SAD rats to aortic coarctation. The hypertensive response after sustained (45-min) aortic coarctation in untreated SAD and intact rats is shown in Fig. 1, top. Basal mean carotid pressure (MCP) measured before aortic coarctation did not differ between groups (107 ± 1 vs. 116 ± 4 mmHg in SAD rats). Five minutes after aortic coarctation, MCP had already reached a plateau and remained close to this level throughout the experimental period (45 min). However, the increase in MCP was much higher in SAD than in intact rats (170 ± 4 vs. 147 ± 2 mmHg 5 min after coarctation). The corresponding HR of both groups before and after aortic coarctation is shown in Fig. 1, bottom. The basal HR before aortic coarctation was higher in SAD rats (470 ± 13 beats/min) than in intact rats (369 ± 6 beats/min). However, whereas intact rats presented a conspicuous and maintained reflex bradycardia after coarctation, the HR of SAD rats did not change throughout the period of observation regardless of the increase in pressure elicited by aortic coarctation.

View larger version (15K): [in this window] [in a new window]   Fig. 1.   Effect of partial aortic coarctation on mean carotid pressure (top) and heart rate (bottom) in conscious unrestrained intact () and sinoaortic-denervated () rats. * P < 0.05 compared with corresponding point in intact group.

View larger version (15K): [in this window] [in a new window]   Fig. 2.   Effect of partial aortic coarctation on mean carotid pressure (top) and heart rate (bottom) in conscious unrestrained guanethidine-treated (50 mg · kg1 · day1 ip for 5 wk) intact () and sinoaortic-denervated () rats. * P < 0.05 compared with corresponding point in intact group.

Effect of prazosin on hypertensive response of SAD rats to aortic coarctation. The effect of the ₁-receptor antagonist prazosin on the hypertensive response of SAD and intact rats to aortic coarctation is shown in Fig. 3, top. The increase in MCP after 10 min of aortic coarctation was significantly greater in SAD rats (from 116 ± 6 to 179 ± 4 mmHg) than in intact rats (from 108 ± 3 to 150 ± 2 mmHg). Prazosin injected intravenously did not affect the hypertensive response of intact rats, which remained stable up to the end of the experimental period. In contrast, after prazosin the MCP of SAD rats declined rapidly to values similar to those for the intact group. The corresponding time course of HR for these groups is shown in Fig. 3, bottom. As observed earlier, the basal HR was higher in SAD rats (418 ± 15 beats/min) than in intact rats (329 ± 11 beats/min). The reflex bradycardia of intact rats was not affected by prazosin, and the HR of SAD rats was not affected by the increase in MCP after aortic coarctation or by prazosin.

View larger version (17K): [in this window] [in a new window]   Fig. 3.   Effect of prazosin (arrow) on mean carotid pressure (top) and heart rate (bottom) responses to partial aortic coarctation in conscious intact () and sinoaortic-denervated () rats. * P < 0.05 compared with corresponding point in intact group.

	DISCUSSION

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The present study confirms our previous reports showing that partial aortic constriction proximal to the renal arteries elicited a prompt and sustained (45-min) rise in MCP associated with a stable reflex bradycardia in conscious intact rats (16, 17). On the other hand, SAD rats presented a higher hypertensive response without reflex bradycardia. The maintenance of MCP at ~170 mmHg in SAD rats during a period of 45 min without any change in HR indicated total sinoaortic deafferentation.

To compare the role of sympathetic activity in the hypertensive response to aortic constriction in SAD and intact rats, the experiments were performed on animals submitted to chronic (5-wk) sympathectomy with guanethidine or acute ₁-adrenergic receptor blockade with prazosin. Basal MCP and HR were not affected by 5 wk of treatment with guanethidine in intact or SAD rats, confirming previous reports (9). Chronically sympathectomized SAD rats showed a lower hypertensive response to aortic constriction than untreated rats; in fact, they exhibited a hypertensive response similar to that of intact rats but unaccompanied by reflex bradycardia. These findings suggest that the higher hypertensive response of SAD rats involves an effective contribution by sympathetic nervous activity. It is also noteworthy that chronically sympathectomized intact rats exhibited a hypertensive response and reflex bradycardia similar to those observed in untreated intact rats. It has been demonstrated that chronic administration of guanethidine to adult rats depletes only tissue cathecolamines for several months after the end of the treatment (6). Therefore, the occurrence of reflex bradycardia in chronically sympathectomized rats indicates that baroreceptor afferents as well as vagal efferents were unaffected by guanethidine treatment.

In the model of abdominal aortic coarctation hypertension, the kidneys are under low perfusion pressure so that a sympathoexcitatory vasoconstrictor reflex (renal pressor reflex) can be triggered (2-4). As observed with stenosis of the renal artery in conscious rats, suprarenal aortic constriction may activate renal R₂ chemoreceptors (13, 14) by decreasing glomerular filtration rate and tubular fluid flow (1). This mechanism would trigger a renal pressor reflex, which causes sympathetic activation and a sustained increase in blood pressure, particularly in the absence of baroreflex. The fact that chronic sympathectomy blunted the enhanced hypertensive response to aortic constriction observed in the absence of the sinoaortic baroreceptors indicates that the sympathetic nervous system contributes to the hypertensive response of SAD rats.

The role of sympathetic activity during aortic coarctation in conscious SAD and intact rats was also examined by the acute administration of the ₁-receptor antagonist prazosin. Thus prazosin reduced the hypertensive response of SAD and intact rats to the same level, which is consistent with the findings obtained for chronically sympathectomized SAD rats. Likewise, the lack of effect of prazosin on the hypertensive response of rats with intact arterial baroreceptors supports the hypothesis of an efficient role for the arterial baroreceptors in buffering the pressor response to aortic coarctation by inhibition of the sympathetic nervous system. We previously (18) demonstrated that conscious intact animals exhibited a significant decrease in plasma norepinephrine levels during 45 min of aortic coarctation. This finding indicated that sympathetic nervous activity was effectively attenuated by the arterial baroreceptors, with this vasopressor system playing no role in this model of hypertension when the arterial baroreceptors are intact. The similarity of the pattern of hypertensive response observed with chronic sympathectomy (guanethidine) and acute ₁-receptor blockade (prazosin) precludes any secondary effect, e.g., fluid balance and altered vessel responsiveness to agonists, that might be caused by chronic guanethidine treatment.

In considering the pathophysiological implications of the data obtained in the present study, it is of interest that the sympathetic nervous system participates as a short-term regulator of arterial pressure and hypertension (10). In fact, it has been shown that young mildly hypertensive patients (10) and patients with established renovascular hypertension (22) display elevated sympathetic nervous system activity.

In conclusion, the data obtained in the present study by combining sinoaortic deafferentation with chronic sympathectomy with guanethidine or acute ₁-receptor blockade with prazosin indicate that the greater hypertensive response of SAD rats involves sympathetic activation, unmasked by the removal of the arterial baroreceptors, in the maintenance of the rise in pressure due to aortic coarctation. In addition, the results also highlight the importance of the arterial baroreceptors in preventing increases in sympathetic drive triggered by different stimuli such as low renal perfusion pressure.