Losartan and enalapril therapies enhance vasodilatation in the mesenteric artery of spontaneously hypertensive rats.
We studied the effects of 10-week long enalapril and losartan treatments (4 and 15 mg kg(-1) day(-1), respectively) on mesenteric arterial function in vitro in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The relaxations of noradrenaline-precontracted rings to acetylcholine, nitroprusside and cromakalim were similar in WKY and enalapril- and losartan-treated SHR, and more pronounced than in untreated SHR. The responses to acetylcholine were attenuated by N(G)-nitro-L-arginine methyl ester in WKY and drug-treated SHR, but were completely inhibited in untreated SHR. When hyperpolarization of smooth muscle was prevented by KCl-induced precontractions, no differences were found in the relaxations to acetylcholine and nitroprusside between the groups, and the dilatations to cromakalim were abolished. Moreover, in noradrenaline-precontracted rings of drug-treated SHR, the addition of tetraethylammonium attenuated the nitric oxide synthase and cyclooxygenase-resistant relaxations to acetylcholine and abolished the enhanced dilatations to nitroprusside. In conclusion, since the enhancement of vasorelaxation in enalapril- and losartan-treated SHR was abolished by conditions preventing hyperpolarization, the improved vasodilatation following these therapies could be attributed to enhanced vasodilatation via K+ channels in this model of hypertension.
Kähönen
M
M
Department of Pharmacological Sciences, University of Tampere, Tampere University Hospital, Finland.
Tolvanen
J P
JP
Kalliovalkama
J
J
Wu
X
X
Karjala
K
K
Mäkynen
H
H
Pörsti
I
I
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004008:Diclofenac / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology* / Q000627:therapeutic use; D004727:Endothelium / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D004008:Diclofenac; D011189:Potassium Chloride; D004656:Enalapril; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester