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Captopril therapy decreases both expression and function of α1D-adrenoceptors in pre- hypertensive rat aorta

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1 The effects of captopril on α1-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 pA2 values for BMY 7378, an α1D-adrenoceptor antagonist, were 8.63–9.20 among the different groups. Schild slopes were close to unity suggesting that contraction was produced primarily by α1D-adrenoceptor stimulation and was not changed with therapy.

4α1D-Adrenoceptor mRNA and protein values were higher in pre-hypertensive SHR than in WKY, whereas α1A-adrenoceptor mRNA was higher in WKY and α1B-adrenoceptors were similar in both strains, and protein was not significantly different for α1A- and α1B-subtypes.

5 Captopril decreased maximal contraction in SHR, without having effect in WKY rats, while α1D-adrenoceptor mRNA was decreased in both rat strains but α1D-adrenoceptor protein was significantly decreased only in SHR, and increased α1A-mRNA in SHR, no effect of captopril treatment was observed on α1B-adrenoceptor mRNA and protein nor on α1A-adrenoceptor protein.

6 These data suggest that ACE inhibition by captopril influences both expression and function of α1D-adrenoceptors in aorta of pre-hypertensive rats, probably avoiding α1D-subtype expression by blockade of angiotensin II synthesis.

Keywords: captopril; contraction; mRNA; protein; spontaneously hypertensive rats; α1D-adrenoceptors

Document Type: Research Article


Affiliations: 1: Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados-Sede Sur, México, D.F. 2: Escuela Superior de Medicina-Instituto Politécnico Nacional, México, D.F.

Publication date: January 1, 2006


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