Vasoconstrictor Role of Vasopressin and Angiotensin in Experimental Aortic Stenosis in the Rat

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Abstract
The roles of vasopressin and angiotensin II in the regulation of peripheral vascular tone were investigated in control rats and in rats with chronic (15 weeks) aortic stenosis, by intravenous application of a specific antagonist to the vascular receptors of vasopressin and the angiotensin-converting enzyme inhibitor teprotide. The application of a Silver clip (0.6 mm) on the aorta ascendens produced a hemodynamically effective aortic stenosis with an increase in left ventricular weight (38%), a reduction in mean arterial pressure, cardiac index, and stroke volume index, and an increase in peripheral vascular resistance. In both groups of rats, a bolus injection of 30 μg of the vasopressin inhibitor d (CH2) 5 Tyr (Me) arginine vasopressin (AVP) showed an agonistic effect by increasing arterial pressure by 11 and 15 mm Hg, respectively, and no antagonistic effect in the control animals. In the rats with chronic aortic stenosis we observed a significant fall in blood pressure (4.1 ± 5.5 mm Hg; p < 0.05) and a reduction in peripheral vascular resistance of 6.3% (p < 0.02). Stroke volume index and heart rate did not change. Most of the animals with aortic stenosis had inappropriately elevated plasma levels of vasopressin and increased levels of plasma renin concentration. The rats with aortic stenosis and inappropriately increased values of vasopressin showed significantly lower plasma osmolality, cardiac index, and stroke volume index and increased peripheral vascular resistance compared with the stenosed rats with a normal osmoregulation of vasopressin. Following the injection of teprotide, there was a greater fall in mean arterial pressure (−18.6 ± 10.8 mm Hg; p < 0.001) than after treatment with the AVP inhibitor and a marked reduction of peripheral resistance (−24%; p < 0.001), indicating a greater importance of the renin-angiotensin system in the regulation of vascular tone.

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