Hydrogen sulfide: regulatory role on blood pressure in hyperhomocysteinemia

Hyperhomocysteinemia (HHcy) is a metabolic disorder marked by an excess amount of the amino acid homocysteine (Hcy) in the blood stream. Hcy is a H(2)S precursor-formed from the metabolism of methionine. Elevated Hcy levels have been associated with higher blood pressure. However, the precise contribution of H(2)S to blood pressure in HHcy is not known. In the current study, we have examined a novel link between H(2)S, blood pressure and HHcy. Male Sprague-Dawley rats were injected with PAG, NaHS, L-NAME+PAG and saline. HHcy condition was induced by providing methionine (1 g/kg) in drinking water for 8 weeks. After 8 weeks, plasma Hcy and H(2)S were measured. The treated rats were anaesthetized with a mixture of ketamine hydrochloride and medetomidine. Blood pressures were measured by intra-carotid artery catheterization and to further investigate the immediate effect of NO and H(2)S, exogenous drugs namely NaHS, SNP, Ach and NA were administered. Plasma Hcy levels were higher in HHcy groups and this group exhibited hypertension. We observed high blood pressure at low levels of H(2)S and vice versa. Endogenous H(2)S in HHcy condition facilitated a mild decrease in MAP (Mean Arterial Pressure). Exogenous SNP (NO donor) showed a greater pressure decrease in HHcy group. The underlying mechanism is yet to be exploited. High levels of Hcy play an important role in the pathogenesis of hypertension. The results suggest that both endogenous and exogenous H(2)S may play a vital role in regulating blood pressure in HHcy.