Cardiovascular effects of a renin inhibitor in relation to posture in nonhuman primates.
Orthostatic cardiovascular reflexes were evaluated in conscious cynomolgus monkeys during interruption of the renin-angiotensin system with the renin inhibitor: RIP (Pro-His-Pro-Phe-His-Phe-Phe-Val-Tyr-Lys-OH). RIP was synthesized via solid phase techniques and purified to homogeneity. In vitro studies indicated that it exhibited classical competitive inhibition of renin with a KI of 2.3 microM. In vivo, RIP at 2 mg/kg per min inhibited renin and angiotensin I pressor responses indicating that it was not a specific renin inhibitor at this dose. However, in spite of the nonspecificity, RIP did not affect the supine blood pressure of sodium-replete monkeys, but did evoke hypotension in supine sodium depleted monkeys. RIP did not elicit significant orthostatic hypotension in either sodium-replete or sodium depleted monkeys. The cardiovascular effects of RIP described in this study appear to be due to inhibition of the renin-angiotensin system.
Pals
D T
DT
DeGraaf
G L
GL
Kati
W M
WM
Lawson
J A
JA
Smith
C W
CW
Skala
G F
GF
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D006801:Humans; D007024:Hypotension, Orthostatic / Q000139:chemically induced; D008252:Macaca fascicularis; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology* / Q000633:toxicity; D011187:Posture; D012018:Reflex / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012504:Saralasin / Q000494:pharmacology; D012964:Sodium / Q000008:administration & dosage / Q000172:deficiency; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D009842:Oligopeptides; D012504:Saralasin; D012964:Sodium; D000092502:Renin Inhibitors; C027509:renin inhibitory peptide