Soluble and particulate guanylate cyclases cooperatively regulate cGMP-mediated relaxation in human and murine vascular tissue, with increased ANP sensitivity after NO synthesis inhibition.
Does the interaction between soluble and particulate guanylate cyclase pathways cooperatively regulate cGMP-mediated vasorelaxation in vascular tissue?
Soluble and particulate guanylate cyclases cooperatively regulate cGMP-mediated vasorelaxation, which may have important implications for pathophysiologies involving NO or ANP deficiency and the clinical use of nitrovasodilators.
Nitric oxide (NO) and atrial natriuretic peptides (ANP) activate soluble (sGC) and particulate guanylate cyclase (pGC), respectively, and play important roles in the maintenance of cardiovascular homeostasis. However, little is known about potential interactions between these two cGMP-generating pathways. Here we demonstrate that sGC and pGC cooperatively regulate cGMP-mediated relaxation in human and murine vascular tissue. In human vessels, the potency of spermine-NONOate (SPER-NO) and ANP was increased after inhibition of endogenous NO synthesis and decreased by prior exposure to glyceryl trinitrate (GTN). Aortas from endothelial NO synthase (eNOS) knockout (KO) mice were more sensitive to ANP than tissues from wild-type (WT) animals. However, in aortas from WT mice, the potency of ANP was increased after pretreatment with NOS or sGC inhibitor. Vessels from eNOS KO animals were less sensitive to ANP after GTN pretreatment, an effect that was reversed in the presence of an sGC inhibitor. cGMP production in response to SPER-NO and ANP was significantly greater in vessels from eNOS KO animals compared with WT animals. This cooperative interaction between NO and ANP may have important implications for human pathophysiologies involving deficiency in either mediator and the clinical use of nitrovasodilators.
Hussain et al. (Thu,) reported a other. sGC and pGC pathway modulators (SPER-NO, ANP, GTN, NOS/sGC inhibitors) vs. Untreated vessels or wild-type mice was evaluated on cGMP-mediated vasorelaxation and cGMP production. Soluble and particulate guanylate cyclases cooperatively regulate cGMP-mediated relaxation in human and murine vascular tissue, with increased ANP sensitivity after NO synthesis inhibition.
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