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1 Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA
2 Department of General Surgery, Wake Forest University School of Medicine, Winston-Salem, NC, USA
* To whom correspondence should be addressed. E-mail: cferrari{at}wfubmc.edu.
When increased in vascular tissues, angiotensin converting enzyme 2 (ACE2), a carboxypeptidase that hydrolyzes angiotensin II to angiotensin-(1-7), may augment the growth inhibitory and vasodilatory effects of the heptapeptide. We investigated the regulation of ACE2 and angiotensin-(1-7) expression in aortas and carotid arteries of male 12 week old spontaneously hypertensive rats (SHR) by determining the effect of sustained AT1 receptor blockade with olmesartan (10 mg/kg/day, n = 13) compared to those that received atenolol (30 mg/kg/day, n = 13), hydralazine (10 mg/kg/day, n = 13) or vehicle (n = 21). Systolic blood pressures were approximately 30% lower (p < 0.05) in rats treated for two weeks with olmesartan compared to vehicle-treated rats. Both atenolol and hydralazine produced similar decreases in systolic blood pressure. ACE2 mRNA in the thoracic aorta of olmesartan-treated rats (n = 8) was five-fold greater (p < 0.05) than in vehicle-treated rats (n = 16), whereas atenolol (n = 8) or hydralazine (n = 8) had no effect. Immunostaining intensities in rats treated with olmesartan (n = 5) was also associated with increased (p < 0.05) ACE2 and angiotensin-(1-7) in the thoracic aorta media compared to vehicle-treated rats. In contrast, immunostaining intensities for both ACE2 and angiotensin-(1-7) were not different from vehicle (n = 5) in the carotid arteries of SHR medicated with either atenolol (n = 5) or hydralazine (n = 5). Comparison of vessel wall dimensions showed that olmesartan selectively reduced the thoracic aorta media/lumen ratio (p < 0.05) and media thickness (p < 0.05) without effect on carotid artery morphometry. Compared to vehicle-treated SHR, vascular hypertrophy determined from media and lumen measurements was not changed in SHR given either atenolol or hydralazine. These data represent the first report of ACE2 and angiotensin-(1-7) expression in aorta and carotid arteries of SHR. Increased ACE2 and angiotensin-(1-7) in association with altered dimensions of the thoracic aorta but not carotid arteries in response to olmesartan treatment provides evidence that this pathway is regulated by AT1 receptors and may be important in mediating the pressure-independent vascular remodeling effects of angiotensin peptides.
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