Hydrogen Sulfide and Nitric Oxide Improve Renal Function and α-Adrenergic Responsiveness in Rats with Left Ventricular Hypertrophy.

In left ventricular hypertrophy (LVH), the combined external administration of hydrogen sulfide (H2S) and nitric oxide (NO) has been shown to reverse LVH by activating the endothelial nitric oxide synthase pathway (eNOS/NO), independent of the cystathionine γ-lyase (CSE/H2S) pathway. Individually, both H2S and NO have also been reported to significantly improve RCBP, restore renal excretory performance, and enhance α-adrenergic receptor responsiveness in rats. The induction of LVH was performed over a period of two weeks using drinking water with caffeine and isoprenaline. Five weeks later, the rats were fed with L-arginine (1.25 g/L) as a nitrogen oxide donor. Vascular reactions to methoxamine, phenylephrine, and noradrenaline were assessed in presences and absence of 5-methylurapidil (5-MeU), BMY7378, and chloroethylclonidine (CeC) and α1-adrenoceptor antagonists. In both the Control WKY and LVH-WKY groups, combined H2S+NO therapy significantly (p < 0.05) upregulated the renal mRNA of CSE and eNOS when compared with untreated LVH rats. The treatment also markedly increased RCBP in LVH-H2S+NO rats relative to LVH controls. Furthermore, H2S+NO administration enhanced the activity of α1A, α1B, and α1D adrenergic receptors in mediating renal vasoconstriction. Even under receptor blockade with high doses (HDs) of 5-MeU, CeC, and BMY 7378, renal vasoconstriction responses to adrenergic agonists like NA, PE, and ME in the LVH-H2S+NO group remained comparable to those observed in the counterpart Control-H2S+NO group. The findings of current study suggest that simultaneous exogenous administration of H2S and NO donors improve renal cortical blood flow, support renal function, and augment α1A, α1B, and α1D adrenergic receptor responsiveness to adrenergic agonists like NA, PE, and ME in LVH rats. This effect appears to rely primarily on the eNOS/NO pathway, with partial contribution from the CSE/H2S pathway.