The effect of intravenous recombinant human renin on blood pressure in pithed spontaneously hypertensive rats.
The effect of highly purified recombinant human renin (rh-renin), expressed in Chinese hamster ovary cells, on mean blood pressure (MBP) was evaluated in pithed spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Intravenous bolus injection of rh-renin produced dose-dependent increases in MBP in pithed SHR and WKY. The pressor response to rh-renin in pithed SHR was about 3 times as potent as that in pithed WKY. Intravenous infusion of rh-renin produced dose-dependent progressive increases in MBP during the first 40 min, reaching plateaus and thereafter MBP was maintained up to 120 min. This hypertensive response to rh-renin was antagonized by renin inhibitors, YM-21095 and KRI-1314, which inhibited the reaction between rh-renin and tetradecapeptide competitively, with Ki values of 5.1 x 10(-10) and 4.3 x 10(-9) M, respectively. In rh-renin-infused pithed SHR, the hypotensive effect of YM-21095 was 37 times as potent as that of KRI-1314. These results suggest that rh-renin can stimulate the rat renin-angiotensin system, thereby producing hypertension. Moreover, the rh-renin-infused rat model could be useful to evaluate the effect of renin inhibitor.
Shibasaki
M
M
Medicinal Research Laboratories II, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Sudoh
K
K
Asano
M
M
Murakami
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D016466:CHO Cells; D006224:Cricetinae; D003655:Decerebrate State / Q000503:physiopathology; D004151:Dipeptides / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012083:Renin / Q000008:administration & dosage / Q000494:pharmacology*; D000092502:Renin Inhibitors
D004151:Dipeptides; D009025:Morpholines; D009281:Naphthalenes; D011994:Recombinant Proteins; D012083:Renin; D000092502:Renin Inhibitors; C074794:YM 21095; C060500:KRI 1314