Angiotensin and sodium balance: their role in chronic two-kidney Goldblatt hypertension.
The purpose of this study was twofold: 1) to determine whether the failure of rats with chronic renovascular hypertension to respond to the angiotensin II antagonist (AIIA) with a decrease in mean blood pressure (BP) was dur to the agonistic effect of the antagonist; and, 2) if this was not the case, to examine whether a positive sodium balance impaired the reversal of the hypertension, after unclamping, in the rats that did not respond to angiotensin inhibitors. For this purpose, rats with chronic, two-kidney Goldblatt hypertension (one renal artery clamped and contralateral untouched) were tested for their BP response to the AIIA (1-Sar-8-Ala-angiotensin II) and to the converting enzyme inhibitor (CEI) SQ20,881, which is devoid of agonistic effect. Approximately 50% of the rats responded to both inhibitors either with no change or with a decrease in BP of less than 20 mm Hg (nonresponders). The other 50% had a decrease in BP of 20 mm Hg or greater (responders). The decrease in BP produced by the AIIA and the CEI correlated significantly (r = 0.76). Nonresponders to both inhibitors were unclamped or sham unclamped. A positive sodium balance was produced before surgery by injecting either 400 or 1000 microEq of sodium and was maintained for 12 hours. Direct BP significantly decreased 12 hours after surgery in the unclamped rats despite a continuous positive sodium balance. In the sham unclamped rats, BP did not change. These data indicate that the failure to respond to the AIIA is not due to the agonistic effect of this peptide. Furthermore, these data suggest that a positive sodium balance is not a major pathogenetic factor in maintaining the high BP in the nonresponder rats, since a positive sodium balance failed to maintain the hypertension after unclamping.
D000809:Angiotensins / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006977:Hypertension, Renal / Q000209:etiology*; D006978:Hypertension, Renovascular / Q000209:etiology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology / Q000502:physiology; D010530:Peritoneal Dialysis; D051381:Rats; D012964:Sodium / Q000378:metabolism*
D000809:Angiotensins; D012964:Sodium; D007703:Peptidyl-Dipeptidase A