Mechanism of ergonovine-induced contraction in the mesenteric artery from deoxycorticosterone acetate-salt hypertensive rat.
Contractile responsiveness of the rat mesenteric artery to the ergot alkaloid ergonovine is enhanced in deoxycorticosterone acetate (DOCA) hypertension. This study determines if this abnormality is mediated through serotonergic or alpha adrenergic receptors and investigates the cellular mechanism of the contraction. Mesenteric arteries were dissected from DOCA hypertensive and normotensive rats for use in isolated tissue experiments. Contractions to 5-hydroxytryptamine, phenylephrine, norepinephrine, dopamine and histamine were of a similar maximum in the hypertensive and sham artery with phenylephrine, dopamine and serotonin more potent in hypertension. Ergonovine contracted hypertensive arteries (maximum = 245 +/- 27 mg) but only minimally in sham arteries (maximum = 83 +/- 19 mg). Endothelium removal did not enhance contraction to ergonovine. The alpha-1 antagonist prazosin (10(-6) M) and the serotonergic antagonist 1-naphthylpiperazine (10(-6) M) shifted the ergonovine concentration response of the hypertensive artery rightward. The alpha-2 receptor antagonist idazoxan (10(-6) M) and dopamine antagonist haloperidol did not affect contraction to ergonovine. Contraction to ergonovine was not altered by indomethacin or 2-nitro-4-carboxyphenyl-N,N-diphenylcarbamate and was minimally affected by genistein, indicating that ergonovine does not activate pathways which involve cyclooxygenase, phospholipase C or tyrosine kinases, respectively. The protein kinase C inhibitor chelerythrine (10(-5) M), nifedipine (10(-6) M) and calcium-free medium blocked ergonovine-induced contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
Watts
S W
SW
Department of Physiology, University of Michigan, Ann Arbor.
Webb
R C
RC
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003900:Desoxycorticosterone; D004298:Dopamine / Q000494:pharmacology; D004874:Ergonovine / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D012701:Serotonin; D003900:Desoxycorticosterone; D006632:Histamine; D002118:Calcium; D004298:Dopamine; D004874:Ergonovine; D009638:Norepinephrine