Regulation of renal artery smooth muscle tone by α1-adrenoceptors: role of voltage-gated calcium channels and intracellular calcium stores

The ischemia induced vasospasm of the renal arterial blood vessels mediated by α1-adrenoceptors is of importance for the loss of kidney function. This is based on reduced perfusion of the kidney cortex occuring in kidney transplant and organ preserving surgery. The present study considered the intracellular mechanism of the norepinephrine (NE) induced renal artery vasospasm by using swine renal artery smooth muscle ring. Norepinephrine and phenylephrine (PE) induced dose-dependent and fully reversible isometric contractions with a threshold concentration of 10 nM (n=7) and 10 nM (n=4), and an EC50 of 0.3 μM and 1 μM, respectively. The receptor was identified as α1A-subtype. The contraction was completely inhibited by verapamil (IC50=1.51 μM; n=11) and diltiazem (IC50=9.49 μM; n=8) and 85% by nifedipine (IC50=0.13 μM; n=21). Blockade of the intracellular inositol-1,4,5-trisphosphate (IP3)-sensitive Ca2+ store by thapsigargin (1 μM, n=7) or suppression of Ca2+ release from the intracellular Ca2+-sensitive Ca2+ store by ryanodine (100 μM, n=4) inhibited the PE induced contraction by 39.5% and 47.6%, respectively. The results suggest a key role of voltage-dependent Ca2+ channels and intracellular Ca2+ stores in the α1A-adrenoceptor induced contraction of the renal artery.