Captopril therapy decreases both expression and function of alpha-adrenoceptors in pre- hypertensive rat aorta.
1.-- The effects of captopril on alpha(1)-adrenoceptor mRNA and protein and phenylephrine-induced contraction was assessed in aorta of pre-hypertensive spontaneously hypertensive rats. 2.-- Four-week-old SHR and WKY rats were treated with captopril [an angiotensin-converting enzyme (ACE) inhibitor] 3 mg kg(-1) day(-1) for 1 week. 3.-- pA(2) values for BMY 7378, an alpha(1D)-adrenoceptor antagonist, were 8.63-9.20 among the different groups. Schild slopes were close to unity suggesting that contraction was produced primarily by alpha(1D)-adrenoceptor stimulation and was not changed with therapy. 4.-- Alpha(1D)-adrenoceptor mRNA and protein values were higher in pre-hypertensive SHR than in WKY, whereas alpha(1A)-adrenoceptor mRNA was higher in WKY and alpha(1B)-adrenoceptors were similar in both strains, and protein was not significantly different for alpha(1A)- and alpha(1B)-subtypes. 5.-- Captopril decreased maximal contraction in SHR, without having effect in WKY rats, while alpha(1D)-adrenoceptor mRNA was decreased in both rat strains but alpha(1D)-adrenoceptor protein was significantly decreased only in SHR, and increased alpha(1A)-mRNA in SHR, no effect of captopril treatment was observed on alpha(1B)-adrenoceptor mRNA and protein nor on alpha(1A)-adrenoceptor protein. 6.-- These data suggest that ACE inhibition by captopril influences both expression and function of alpha(1D)-adrenoceptors in aorta of pre-hypertensive rats, probably avoiding alpha(1D)-subtype expression by blockade of angiotensin II synthesis.
Godínez-Hernández
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Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, México, D.F.
Gallardo-Ortíz
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IA
López-Sánchez
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Villalobos-Molina
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R
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*
C547715:Adra1a protein, rat; C547721:Adra1d protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D002216:Captopril; C053428:BMY 7378