Why the study?
Does angiotensin antagonism lower blood pressure in sodium-depleted dogs?
Does angiotensin antagonism lower blood pressure in sodium-depleted dogs?
Angiotensin plays both a direct and indirect role in maintaining blood pressure during sodium depletion, as demonstrated by the blood pressure-lowering effects of converting enzyme inhibitors and angiotensin antagonists without triggering homeostatic reflexes.
BP reduction by CEI or angiotensin antagonist scales with log renin activity without reflex tachycardia in dogs; leaves open human translation.
Sodium depletion was induced in dogs to raise plasma renin activity (PRA) from 1.11 to 26.48 ng/ml/hr. Little overall change in blood pressure (BP) occurred, but cardiac output (CO) and central venous pressure fell, while total peripheral resistance and heart rate (HR) increased. A nonapeptide converting enzyme inhibitor (CEI) produced a fall in BP which was linearly related to log. PRA; the intercept with PRA was at 1.05 ng/ml/hr, close to the average value for dogs on a normal diet. The fall in BP with this agent was not accompanied by an increase in HR or CO. When Sar1-Ala8 angiotensin II was used to antagonize the action of angiotensin, the fall in BP was also linearly related to log. PRA. However, for a given level of PRA this fall in BP was less than that achieved with CEI and the intercept of BP fall with PRA was 2.6 ng/ml/hr. Again with this agent there was little change in HR or CO as BP was reduced. Thus, both antagonists lowered peripheral resistance without exciting the homeostatic reflexes indicating that, as PRA rose above the normal resting level, the angiotensin generated had both a direct and indirect effect in maintaining BP.
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Conway et al. (1979) studied this question.
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