Captopril therapy decreases both expression and function of α_1D-adrenoceptors in pre- hypertensive rat aorta

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 α_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 α_1D- adrenoceptor stimulation and was not changed with therapy. 4 α_1D-Adrenoceptor mRNA and protein values were higher in pre-hypertensive SHR than in WKY, whereas α_1A-adrenoceptor mRNA was higher in WKY and α_1B-adrenoceptors were similar in both strains, and protein was not significantly different for α_1A- and α_1B-subtypes. 5 Captopril decreased maximal contraction in SHR, without having effect in WKY rats, while α_1D-adrenoceptor mRNA was decreased in both rat strains but α_1D-adrenoceptor protein was significantly decreased only in SHR, and increased α_1A-mRNA in SHR, no effect of captopril treatment was observed on α_1B-adrenoceptor mRNA and protein nor on α_1A-adrenoceptor protein. 6 These data suggest that ACE inhibition by captopril influences both expression and function of α_1D-adrenoceptors in aorta of pre-hypertensive rats, probably avoiding α_1D-subtype expression by blockade of angiotensin II synthesis.