Mechanical load opposes angiotensin-mediated decrease in vascular alpha(1)-adrenoceptors

alpha(1)-Adrenergic receptor contraction of vascular smooth muscle is augmented by increases in angiotensin II and also in several forms of hypertension. Whether angiotensin directly modulates alpha(1)-adrenoceptor subtype expression to contribute to this effect is unknown. In a previous study, we demonstrated that increased mechanical load (pressure) per se does not alter expression of alpha(1B)- and alpha(1D)-adrenoceptors in rat aortic smooth muscle in cell culture, in vitro or in vivo. However, findings in aortic coarctation hypertension suggested that a humoral factor, possibly angiotensin, selectively reduces alpha(1B)-adrenoceptors and that increased mechanical load opposes this decrease. The present study examined this hypothesis by determining the effect of angiotensin alone and in the presence of mechanical loading on the expression of alpha(1D)- and alpha(1B)-adrenergic receptor mRNAs and alpha(1D)-receptor density in cultured aortic smooth muscle cells. alpha(1D) mRNA content, per smooth muscle cell, concentration-dependently decreased after 3 hours of exposure to 0.3 nmol/L to 1 mu mol/L angiotensin but by 24 hours had returned to control levels. In contrast, alpha(1B) mRNA concentration-dependently declined at a later time (24 hours) and remained decreased at 48 hours to 27+/-6% of control with 1 mu mol/L angiotensin. Angiotensin also decreased alpha(1)-adrenoceptor density in a dose-dependent manner. Angiotensin had no effect on cell number in these confluent, quiescent cells but did increase cell protein and total RNA. This cellular hypertrophy and the decreases in alpha(1)-adrenoceptor mRNAs were blocked by the angiotensin type 1 receptor antagonist losartan. Cyclic mechanical loading of smooth muscle cells opposed the angiotensin-mediated hypertrophy and decrease in alpha(1B) mRNA expression and alpha(1)-adrenergic receptor density. These data suggest that angiotensin and intravascular pressure interact to affect cell growth and expression of alpha(1B)-adrenergic receptors by vascular smooth muscle.