Relation between adrenergic neurogenic contraction and alpha 1-adrenoceptor subtypes in dog mesenteric and carotid arteries and rabbit carotid arteries.
1. We examined the distribution of alpha 1-adrenoceptor subtypes and their relation to adrenergic neurogenic contraction induced by electrical transmural stimulation in the dog mesenteric and carotid arteries and the rabbit carotid artery. 2. In the dog mesenteric artery, contraction to noradrenaline was competitively inhibited by HV723 (pKB = 9.37) and prazosin (pKB = 8.40). Pretreatment with chlorethylclonidine (CEC) slightly attenuated only the contractions induced by low concentrations of noradrenaline. Contraction induced by electrical transmural stimulation was inhibited at lower concentrations of HV723 than of prazosin. 3. In the dog carotid artery, contraction to noradrenaline was inhibited with higher affinity by prazosin (pKB = 9.82) than by HV723 (pKB = 8.47). Prazosin was also more potent than HV723 in inhibiting the contraction to electrical stimulation. Pretreatment with CEC markedly attenuated or abolished contraction to noradrenaline and electrical stimulation. 4. In the rabbit carotid artery, prazosin inhibited noradrenaline-induced contraction biphasically (pKB = 9.91 and 8.60). After CEC pretreatment, contraction to noradrenaline was attenuated moderately and the high affinity site for prazosin was abolished. HV723 competitively inhibited the noradrenaline response with a similar pKB value (approximately 8.5) regardless of CEC treatment. Contraction to electrical stimulation was inhibited by prazosin more effectively than by HV723 in preparations not treated with CEC, while it was equipotently inhibited by both antagonists in CEC-treated preparations. 5. These results suggest that the contractions induced by endogenous and exogenous noradrenaline are mediated through the same subtypes of alpha,-adrenoceptor distributed in each artery; according to our recent subclassification: alpha 1N subtype in the dog mesenteric artery, alpha 1H subtype in the dog carotid artery and alpha lH and alpha 1L subtypes in the rabbit carotid artery. Different susceptibility to alpha l-adrenoceptor antagonists of sympathetic adrenergic responses in various blood vessels may be related to heterogeneous involvement of distinct alpha,-adrenoceptor subtypes in the sympathetic response.
Department of Pharmacology, Fukui Medical School, Japan.
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Muramatsu
D000097:Acetonitriles / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002339:Carotid Arteries / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000294:innervation*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D013564:Sympathetic Nervous System / Q000502:physiology*
D000097:Acetonitriles; D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; C058562:HV 723; C051731:chlorethylclonidine; D003000:Clonidine; D009638:Norepinephrine; D011224:Prazosin