The long-term effect of captopril treatment on endothelial function in spontaneously hypertensive rats.
The aim of this study is to elucidate the long term effect of captopril treatment on the endothelial function to release nitric oxide (NO) in spontaneously hypertensive rats (SHR). The properties of endothelium were determined with a model of hindquarter perfusion in response to alpha 1 adrenergic agonist, phenylephrine, at the age of 40 weeks of SHR which was administrated with captopril (100 mg/kg/day) from intrauterine and withdrawn at 16 weeks of age. Furthermore, in the presence of N omega-nitro-L-arginine methyl ester (LNAME), or L-arginine, the responses to phenylephrine were studied. From the curve of perfusion pressure, the minimal, maximal perfusion pressure (PPmin, PPmax) and the maximal slope (slope), as well as the 50% of effective concentration (EC50) were obtained. The data show that in captopril treated SHR, PPmin, PPmax and slope were markedly lower, but EC50 higher than those of untreated SHR. The curve induced by phenylephrine was significantly right shift compared with that of untreated SHR. Like WKY, the intensive reactivity to phenylephrine in the presence of LNAME was much lower than that of untreated SHR. In the presence of L-arginine, however, the right shift of curves was seen only in captopril treated SHR and WKY rats, but not in control SHR. In conclusion, endothelium does involve in the response of resistant vessel to phenylephrine. The mechanism of enhanced reactivity in untreated SHR may be, at least in part, due to the diminished capacity of producing NO from endothelium, and the effect of sustained hypotension of early captopril treatment might be relevant to the improved ability of endothelium.
Jin
X
X
Hypertension Division, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005.
Chen
D
D
Wang
H
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D009569:Nitric Oxide; D002216:Captopril