The cellular mechanisms of hydralazine-induced relaxation were investigated in isolated mesenteric resistance arteries from pregnant rats. Administration of hydralazine relaxed phenylephrine-constricted mesenteric arteries with an EC50 of 3.6±0.3μM and an efficacy of 75±6.2%. These vasodilatory effects were abolished by: (1) preconstriction with a potassium depolarizing solution, (2) endothelial denudation (for concentrations of hydralazine<10μM), (3) addition of non-selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors, and (4) pretreatment with a prostacyclin receptor antagonist (R01138452). Nitric oxide synthase (NOS) inhibition did not significantly alter the sensitivity or magnitude of the vasodilatory response; surprisingly, exposure to hydralazine also did not elevate endothelial cell Ca2+, suggesting a novel mechanism of activation. In summary, hydralazine is a potent resistance artery vasodilator that affects both endothelial and vascular smooth muscle (VSM) cells in a concentration-dependent manner. At clinically relevant concentrations (<10μM), its effects in the splanchnic resistance vasculature are: (1) primarily endothelial in origin, require (2) hyperpolarization and (3) activation of COX, and (4) are mediated by the PGI2 (IP) receptor.
Mechanism of hydralizine-induced relaxation in resistance arteries during pregnancy: Hydralazine induces vasodilation via a prostacyclin pathway
MANDALA', Maurizio;
2016-01-01
Abstract
The cellular mechanisms of hydralazine-induced relaxation were investigated in isolated mesenteric resistance arteries from pregnant rats. Administration of hydralazine relaxed phenylephrine-constricted mesenteric arteries with an EC50 of 3.6±0.3μM and an efficacy of 75±6.2%. These vasodilatory effects were abolished by: (1) preconstriction with a potassium depolarizing solution, (2) endothelial denudation (for concentrations of hydralazine<10μM), (3) addition of non-selective cyclooxygenase-1 and cyclooxygenase-2 inhibitors, and (4) pretreatment with a prostacyclin receptor antagonist (R01138452). Nitric oxide synthase (NOS) inhibition did not significantly alter the sensitivity or magnitude of the vasodilatory response; surprisingly, exposure to hydralazine also did not elevate endothelial cell Ca2+, suggesting a novel mechanism of activation. In summary, hydralazine is a potent resistance artery vasodilator that affects both endothelial and vascular smooth muscle (VSM) cells in a concentration-dependent manner. At clinically relevant concentrations (<10μM), its effects in the splanchnic resistance vasculature are: (1) primarily endothelial in origin, require (2) hyperpolarization and (3) activation of COX, and (4) are mediated by the PGI2 (IP) receptor.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.