Objective: 

Sympathetic denervation leads to vascular catecholamine supersensitivity. We tested the hypothesis that mechanisms involved in Ca²⁺ signaling and regulation of Ca²⁺ sensitivity in vascular smooth muscle contribute to denervation supersensitivity.^^

Methods: 

Male and female Wistar rats underwent neonatal sympathectomy. Renal and mesenteric resistance arteries were isolated from 16-week-old animals and used for myography and gene expression analyses.

Results: 

Renal and mesenteric resistance arteries from sympathectomized animals showed significantly higher sensitivity to norepinephrine than control vessels (n = 8–10 per group). In renal but not in mesenteric arteries from sympathectomized animals the sensitivity to selective a₁- and a₂-adrenoceptor stimulation was enhanced. Norepinephrine-induced constriction of renal but not of mesenteric resistance arteries was significantly more sensitive to L-type Ca²⁺ channel blockade and Rho-kinase inhibition in vessels from sympathectomized animals than in vessels from control animals. L-type channel activation (S-[-]-BayK8644) elicited a powerful vasoconstriction in renal resistance arteries from sympathectomized but not from control animals. These effects were not gender-dependent. In female but not in male rats neonatal sympathectomy significantly increased renal resistance artery mRNA expression of the Cav1.2 a₁ subunit and of Rho kinase 1 (60% rise for both genes).

Conclusion: 

The data indicate that different mechanisms contribute to catecholamine supersensitivity in renal and mesenteric resistance arteries. They suggest that Ca²⁺ signaling via L-type Ca²⁺ channels and Ca²⁺ sensitivity of renal resistance arteries depend on sympathetic innervation. Sympathectomy-induced increases in mRNA expression of two proteins involved in Ca²⁺ signaling and regulation of Ca²⁺ sensitivity are gender-dependent.