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

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.

Analysis of erectile responses to bradykinin in the anesthetized rat.

The kallikrein-kinin system is expressed in the corpus cavernosa, and bradykinin (BK) relaxes isolated corpora cavernosal strips. However, erectile responses to BK in the rat have not been investigated in vivo. In the present study, responses to intracorporal (ic) injections of BK were investigated in the anesthetized rat. BK, in doses of 1-100 µg/kg ic, produced dose-related increases in intracavernosal pressure (ICP) and dose-related deceases in mean arterial pressure (MAP). When decreases in MAP were prevented by intravenous injections of angiotensin II (Ang II), increases in ICP, in response to BK, were enhanced. Increases in ICP, ICP/MAP ratio, and area under the curve and decreases in MAP in response to BK were inhibited by the kinin B2 receptor antagonist HOE-140 and enhanced by the angiotensin-converting enzyme (ACE) inhibitor captopril and by Ang-(1-7). Increases in ICP, in response to BK, were not attenuated by the nitric oxide (NO) synthase inhibitor (N(ω)-nitro-L-arginine methyl ester) or the soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) but were attenuated by the cyclooxygenase inhibitor, sodium meclofenamate. Decreases in MAP were not attenuated by either inhibitor. These data suggest that erectile responses are mediated by kinin B2 receptors and modulated by decreases in MAP. These data indicate that ACE is important in the inactivation of BK and that erectile and hypotensive responses are independent of NO in the penis or the systemic vascular bed. Erectile responses to cavernosal nerve stimulation are not altered by BK or HOE-140, suggesting that BK and B2 receptors do not modulate nerve-mediated erectile responses under physiologic conditions. These data suggest that erectile responses to BK are mediated, in part, by the release of cyclooxygenase products.