Pressor response to 1-sar-8-ala-angiotensin II (saralasin) in hypertensive subjects.
An angiotensin II (A II) analogue (1-Sar-8-Ala-angiotensin II) (saralasin) was infused into 418 untreated hypertensive subjects during a 1-day evaluation while blood pressure was recorded every 2 minutes by Arteriosonade. At 5 mug/kg per min, saralasin produced a change in mean blood pressure which correlated significantly (r=-0.54, P less than 0.001) with the stimulated plasma renin activity (PRA) (after intravenous furosemide and ambulation for 2 hours. Saralasin caused a rise inmean blood pressure of at least 7.0 mm Hg in 97 hypertensive subjects, who also had a low stimulated PRA (1.3+/-SEM, 0.1 ng/ml per hour; normal range, 1.7-8.5). On a low sodium diet, the pressor response of hypertensive subjects to saralasin continued and was an even better indicator of a low stimulated PRA. Infusion of saralasin at 10 mug/kg per min into normal subjects on an unrestricted diet, a low sodium diet, and a high sodium diet produced, respectively, no change, a fall (P less than 0.05), and a rise (P less than 0.005) in blood pressure. The same saralasin dose in six hypertensive subjects who showed a pressor response to the analogue in the 1-day study also produced a rise in blood pressure when given on a low sodium diet, and this rise was more than twice that seen in normal subjects on a high sodium diet. Hypertensive subjects who showed the pressor response had a significantly greater (P less than 0.01) pressor sensitivity to A II than did hypertensive nonresponders to saralasin and noraml subjects on an uncontrolled diet. The affinity of the vascular receptors for the analogue was greater in the hypertensive group that showed the pressor response to saralasin. In summary, the pressor response to saralasin, as defined above, occurred in 23% of a large unselected group of hypertensive subjects and was associated with salt loading, a low stimulated PRA, and increased pressor sensitivity to A II.
D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage / Q000031:analogs & derivatives*; D001794:Blood Pressure / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000175:diagnosis*; D007668:Kidney / Q000098:blood supply; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D012504:Saralasin / Q000494:pharmacology*; D012964:Sodium / Q000008:administration & dosage
D000804:Angiotensin II; D012964:Sodium; D003404:Creatinine; D012083:Renin; D012504:Saralasin