The role of angiotensin in the control of blood pressure during sodium depletion.

Abstract

SUMMARY Sodium depletion was induced in dogs to raise plasma renln 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, dose 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 Sar'-Ala' 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 bomeostatic reflexes indicating that, as PRA rose above the normal resting level, the angiotensin generated had both a direct and indirect effect in maintaining BP.

Comparison of renin and converting enzyme inhibition in sodium-deficient dogs.

“…We used Na-deficient dogs because of their highly renin-dependent blood pressure Use of conscious animals obviated activation of the sympathetic nervous system that is frequently observed, especially with barbiturate anesthetics When enalaprilat was administered before SCRIP, MAP was lowered to approximately 70 mm Hg This level of blood pressure is similar to that found by others using Na-deficient dogs 26 or rats 27 with maximally effective doses of ACE inhibitors Thus, 70 mm Hg would appear to be the floor to which MAP can fall in Na-deficient dogs that received ACE inhibitors. Infusing SCRIP into these dogs after having reached this level of MAP produced no further decline in pressure.…”

Angiotensin-converting enzyme inhibitor resets baroreceptor reflexes in conscious dogs.

“…In these experiments, nitroglycerine produced a tachycardia of 60-90 beats/min as it lowered the BP in the saltreplete or salt-depleted dog, while CEI for a similar fall in BP in the salt-depleted dog caused only a small tachycardia of approximately 15 beats/min, as we have previously reported. 10 Thus, during salt depletion the baroreceptor reflex is intact but CEI fails to elicit the reflex as it lowers BP. Since the inhibitor produced a change in baroreflex control only during sodium depletion, this suggests that angiotensin was involved in the maintenance of normal baroreflex function in the salt-depleted dog.…”

“…10 In a total of nine dogs, CEI (0.5 mg/kg) (synthetic nonapeptide, obtained from Beckman, structurally identical to SQ 20,881) was administered before (5 dogs) and after 6-8 days (9 dogs) of sodium depletion. Baroreflex function curves were constructed immediately before and 10 to 30 minutes after these doses of CEI at which times steady-state conditions had been restored.…”

“…In the sodium-depleted dog, we have shown that the fall in BP was proportional to the prevailing level of plasma renin activity (PRA). 10 With both a converting enzyme inhibitor (CEI synthetic nonapeptide) and Sar'-Ala* All, it was noticed that the tachycardia and increase in cardiac output that would normally be expected to accompany a fall in BP did not occur. This has been reported by others in the dog 14 and in man.…”

“…18 ' " We have recently reported that the sympathetically-mediated vasoconstrictor reflex response to reduction in central blood volume is impaired when these inhibitors are used, 10 suggesting that angiotensin may interact physiologically in a subtle way with the sympathetic nervous system to maintain BP.…”