Different effects of acute clenbuterol on vasomotor response in mesenteric arteries from young and old spontaneously hypertensive rats.
We analysed the influence of aging on the acute effect of clenbuterol, a beta(2)-adrenoceptor agonist, on the vasoconstrictor response induced by electrical field stimulation in mesenteric arteries from young and old spontaneously hypertensive rats (SHRs). Clenbuterol increased the contraction elicited by electrical field stimulation in arteries from both groups, and this was prevented by propranolol. N(G)-nitro-L-arginine methyl ester (L-NAME) also increased the electrical field stimulation-elicited contractions in arteries from both age groups. However, pretreatment with capsaicin increased the electrical field stimulation-induced contractions in young SHRs, but did not modify it in old SHRs. In segments from young SHRs, the treatment with the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37), induced an increase in the electrical field stimulation-induced vasoconstrictor response that was not modified by the subsequent addition of capsaicin. Addition of clenbuterol to L-NAME-treated segments from both groups further increased the response to electrical field stimulation. In segments from young SHRs, clenbuterol failed to increase the electrical field stimulation-induced response in the capsaicin-treated segments, but the response was increased by the subsequent addition of L-NAME. The addition of L-NAME to the clenbuterol-treated segments from old SHRs did not modify the enhanced electrical field stimulation response. Electrical field stimulation induced a similar tritium release in arteries from young and old SHRs preincubated with [3H]noradrenaline. In arteries from young SHRs, isoproterenol increased this release and the increase was abolished by propranolol. Clenbuterol increased the stimulated tritium overflow and exogenous noradrenaline response only in segments from old SHRs, and both effects were abolished by propranolol. To summarize and conclude, clenbuterol increased the electrical field stimulation-induced contraction in segments from both age groups. In young SHRs, clenbuterol seems to inhibit CGRP release, while in old SHRs, it increases the release of and response to noradrenaline and decreases neuronal nitric oxide (NO) release.
Ferrer
Mercedes
M
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
Salaices
Mercedes
M
Sánchez
Margarita
M
Balfagón
Gloria
G
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D014316:Tritium; D009599:Nitroprusside; D013779:Tetrodotoxin; D011433:Propranolol; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D002976:Clenbuterol; D010646:Phentolamine