Analysis of cardiovascular responses to the H₂S donors Na₂S and NaHS in the rat

Abstract

Hydrogen sulfide (H2S) is an endogenous gaseous molecule formed from L-cysteine in vascular tissue. In the present study, cardiovascular responses to the H2S donors Na2S and NaHS were investigated in the anesthetized rat. The intravenous injections of Na2S and NaHS 0.03-0.5 mg/kg produced dose-related decreases in systemic arterial pressure and heart rate, and at higher doses decreases in cardiac output, pulmonary arterial pressure, and systemic vascular resistance. H2S infusion studies show that decreases in systemic arterial pressure, heart rate, cardiac output, and systemic vascular resistance are well-maintained, and responses to Na2S are reversible. Decreases in heart rate were not blocked by atropine, suggesting that the bradycardia was independent of parasympathetic activation and was mediated by an effect on the sinus node. The decreases in systemic arterial pressure were not attenuated by hexamethonium, glybenclamide, N(w)-nitro-L-arginine methyl ester hydrochloride, sodium meclofenamate, ODQ, miconazole, 5-hydroxydecanoate, or tetraethylammonium, suggesting that ATP-sensitive potassium channels, nitric oxide, arachidonic acid metabolites, cyclic GMP, p450 epoxygenase metabolites, or large conductance calcium-activated potassium channels are not involved in mediating hypotensive responses to the H2S donors in the rat and that responses are not centrally mediated. The present data indicate that decreases in systemic arterial pressure in response to the H2S donors can be mediated by decreases in vascular resistance and cardiac output and that the donors have an effect on the sinus node independent of the parasympathetic system. The present data indicate that the mechanism of the peripherally mediated hypotensive response to the H2S donors is uncertain in the intact rat.

Pharmacological evidence that NaHS inhibits the vasopressor responses induced by stimulation of the preganglionic sympathetic outflow in pithed rats

“…In anaesthetised rats, i.v. administration of NaHS produced dose-related hypotension (Ali et al, 2006) although the mechanisms are not completely understood (Yoo et al, 2015). In this regard, our results provide evidence that NaHS inhibited sympathetic transmission in the rat systemic vasculature since the experimental model employed allowed to selectively stimulate the preganglionic sympathetic outflow (Gillespie and Muir, 1967).…”

“…Pulse pressure is determined by compliance and ventricular stroke volume. Thus, the effect induced by NaHS is probably due to arterial vasodilatation (Yoo et al, 2015), although we cannot rule out a negative inotropic effect (Geng et al, 2004).…”

“…Indeed, in anaesthetised rats, hypotension to NaHS is not mediated by nitric oxide release, Kþ channels, BKCa channels, cGMP, release of arachidonic acid metabolites or p450 epoxygenase metabolites. This effect was not mediated by adrenergic or cholinergic system since the hypotension to NaHS was unaffected by atropine, phentholamine or hexamethonium (Yoo et al, 2015). Thus, the authors concluded that uncertain mechanisms mediate hypotension to NaHS in anaesthetised rats.…”

“…infusion of NaHS may have blocked vascular α 1 and α 2 -adrenoceptors in the cardiovascular system. However, this possibility is highly unlikely since: (1) phentholamine, a non-selective α 1/2 -adrenoceptor antagonist, failed to block the hypotension to NaHS (Yoo et al, 2015); and (2) NaHS failed to inhibit the vasopressor responses to noradrenaline (Fig. 3) or methoxamine (Fig.…”

Sulfur-containing gaseous signaling molecules

“…Захисну дію справляє у малих дозах H 2 S, у високих може показувати нейротоксичний ефект [22]. Серцево-судинна система є важливим об'єктом дії H 2 S. Як і NO та СО, він розслаблює гладенькі м'язи судин і знижує артеріальний тиск [4,5,13,23], водночас донори H 2 S зменшують кров'яний тиск і частоту серцевих скорочень [24]. Вазодилататорна дія сірководню показана на різних судинах, починаючи з ізольованої аорти і включаючи мезентеріальні артерії людини [25].…”