Blood pressure control: hydrogen sulfide, a new gasotransmitter, takes stage.

Hydrogen sulfide (H2S) is the most recently characterized autocrine/paracrine messenger implicated in the control of vascular tone. A series of coherent observations now document that this gas is a strong vasorelaxant and a determinant of blood pressure in experimental models. Targeted deletion of the gene encoding cystathionine-lyase (CSE). CSE, a key enzyme for H2S biosynthesis, reduces serum H2S levels and determines age-dependent hypertension in mice. Hypertension in this model does not depend on central or on renal mechanisms or on compromised nitric oxide (NO) generation and rests solely on disturbed endothelium dependent vasorelaxation. Cholinergic stimulation of endothelial cells determines a marked increase in H2S levels which can be blocked by the anti-cholinergic drug atropine. H2S has in full the pharmacological properties which are considered characteristics of endothelium relaxing factors. Global endothelium dependent relaxing activity in the CSE knockout mice is reduced by about 60% suggesting that the lack of H2S is critical to explain impaired vasodilatation in these mice. Furthermore arterial pressure is similarly raised in NO synthase knockout and in CSE knockout mice indicating that H2S is a vasoregulator of potency comparable to that of NO. Defective synthesis of H2S may be involved in various human diseases including systemic and pulmonary hypertension and septic shock.