Role of the angiotensin type 1 receptor in modulating the carotid chemoreflex in an ovine model of renovascular hypertension.

Chris Sung-Eun Sohn, Joshua Wen-Han Chang, Bindu George, Siyi Chen, Rohit Ramchandra

Journal of hypertension 2022 Jul 01

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The carotid body has been implicated as an important mediator and putative target for hypertension. Previous studies have indicated an important role for angiotensin II in mediating carotid body function via angiotensin type-1 receptors (AT1R); however, their role in modulating carotid body function during hypertension is unclear. Using a large preclinical ovine model of renovascular hypertension, we hypothesized that acute AT1R blockade would lower blood pressure and decrease carotid body-mediated increases in arterial pressure. Adult ewes underwent either unilateral renal artery clipping or sham surgery. Two weeks later, flow probes were placed around the contralateral renal and common carotid arteries. In both hypertensive and sham animals, carotid body stimulation using potassium cyanide caused dose-dependent increases in mean arterial pressure but a reduction in renal vascular conductance. These responses were not different between groups. Infusion of angiotensin II led to an increase in arterial pressure and reduction in renal blood flow. The sensitivity of the renal vasculature to angiotensin II was significantly attenuated in hypertension compared with the sham animals. Systemic inhibition of the AT1R did not alter blood pressure in either group. Interestingly carotid body-evoked arterial pressure responses were attenuated by AT1R blockade in renovascular hypertension but not in shams. Taken together, our findings indicate a decrease in vascular reactivity of the non-clipped kidney to angiotensin II in hypertension. The CB-evoked increase in blood pressure in hypertension is mediated in part, by the AT1R. These findings indicate a differential role of the AT1R in the carotid body versus the renal vasculature. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Citation

Chris Sung-Eun Sohn, Joshua Wen-Han Chang, Bindu George, Siyi Chen, Rohit Ramchandra. Role of the angiotensin type 1 receptor in modulating the carotid chemoreflex in an ovine model of renovascular hypertension. Journal of hypertension. 2022 Jul 01;40(7):1421-1430