Effects of renin inhibition in the conscious primate Macaca fascicularis.
Pro-His-Pro-Phe-His-Statine-Ile-Phe-NH2 (R-Pep-27), a potent renin inhibitory peptide, was infused into the conscious, sodium-depleted Macaca fascicularis at doses of 0, 0.1, 1, 4, 16, and 32 micrograms/kg/min for 10 minutes. At all doses greater than 0.1 microgram/kg/min, there was a parallel decrease in mean arterial pressure (MAP), plasma renin activity, and plasma angiotensin II (Ang II) concentration. On the other hand, assays with monoclonal antibodies specific for total renin and active renin demonstrated that the peptide's inhibition of circulating active renin stimulated the release of both. The maximal effective R-Pep-27 dose was approximately 16 micrograms/kg/min, which reduced MAP by an average of 15.8 +/- 1.4 mm Hg (n = 14) and plasma renin activity and plasma Ang II concentration to 3% (n = 9) and 15% (n = 5), respectively, of the pretreatment values. At 0.1 microgram/kg/min, there was no significant decrease in MAP; however, measurement of plasma renin activity showed an average decrease in activity of 42% (n = 3). No significant change in the heart rate was observed at all the doses studied. For comparison, intravenous captopril (400 micrograms/kg bolus) was administered after the MAP of the monkeys had recovered from the peptide experiments, and it reduced MAP by 25.1 +/- 2.4 mm Hg (n = 10) without significantly changing plasma renin activity. As anticipated, injection of angiotensin I (80-160 ng/kg bolus) into sodium-depleted monkeys during peptide infusion caused a transient rise in MAP of 14.8 +/- 5.4 mm Hg (n = 4) above the mean pretreatment value.(ABSTRACT TRUNCATED AT 250 WORDS)
Hui
K Y
KY
Massachusetts General Hospital, Boston 02114.
Knight
D R
DR
Nussberger
J
J
Hartley
L H
LH
Vatner
S F
SF
Haber
E
E
D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008253:Macaca mulatta; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology*; D009994:Osmolar Concentration; D012083:Renin / Q000097:blood / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D002216:Captopril; D005665:Furosemide; D009842:Oligopeptides; D012083:Renin; D000092502:Renin Inhibitors; C088339:renin inhibitory peptide, R-PEP-27; C027509:renin inhibitory peptide