Objectives: To investigate whether hypertension could modify the function of adrenergic, nitrergic, and sensory innervations involved in the electrical field stimulation-induced response in mesenteric arteries from female rats.
Methods: Vascular reactivity experiments were performed in endothelium-denuded mesenteric arteries from normotensive, Wistar-Kyoto and spontaneously hypertensive female rats; protein expression was measured by western blot; nitric oxide release was measured by fluorometry; calcitonin gene-related peptide and noradrenaline release were determined by enzyme immunoassay.
Results: The electrical field stimulation-induced contractions were significantly lower in segments from spontaneously hypertensive rats than those of Wistar-Kyoto rats. Hypertension did not modify either the response or release of noradrenaline. Preincubation with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester increased the electrical field stimulation-induced contractions only in segments from Wistar-Kyoto rats. The relaxation induced by the nitric oxide donor sodium nitroprusside was similar in segments from both strains. The electrical field stimulation-induced nitric oxide release was decreased in segments from spontaneously hypertensive rats. The calcitonin gene-related peptide receptor antagonist CGRP(8-37) did not alter the electrical field stimulation-induced contractions in segments from Wistar-Kyoto rats but increased them in segments from spontaneously hypertensive rats. The calcitonin gene-related peptide-induced relaxation was increased in segments from spontaneously hypertensive rats. The expression of the 15-kDa active form of RAMP1 was increased in segments from spontaneously hypertensive rats.
Conclusion: In contrast to male rats, electrical field stimulation-induced contractions are decreased in hypertensive female rats. Nitrergic innervation plays a role in the development and/or maintenance of hypertension, whereas sensory innervation is a counteracting mechanism through the increased calcitonin gene-related peptide response.