Recent research has shown that the endogenous gas hydrogen sulphide (H2S) is a signalling molecule of considerable biological potential and has been suggested to be involved in a vast number of physiological processes. In the vascular system, H2S is synthesized from cysteine by cystathionine-γ-lyase (CSE) in smooth muscle cells (SMC) and 3- mercaptopyruvate sulfuresterase (3MST) and CSE in the endothelial cells. In pulmonary and systemic arteries, H2S induces relaxation and/or contraction dependent on the concentration of H2S, type of vessel and species. H2S relaxes SMC through a direct effect on KATP-channels or Kv-channels causing hyperpolarization and closure of voltage-dependent Ca2+-channels followed by a reduction in intracellular calcium. H2S also relaxes SMC through the release of endothelium- derived hyperpolarizing factor (EDHF) and nitric oxide (NO) from the endothelium. H2S contracts SMC through a reduction in nitric oxide (NO) availability by reacting with NO forming a nitrosothiol compound and through an inhibitory effect on endothelial nitric oxide synthase (eNOS) as well as a reduction in SMC cyclic AMP concentration. Evidence supports a role for H2S in oxygen sensing. Furthermore, reduced endogenous H2S production may also play a role in ischemic heart diseases and hypertension, and treatment with H2S donors and cysteine analogues may be beneficial in treatment of cardiovascular disease.

Endogenous hydrogen sulfide (H 2 S) is involved in the regulation of vascular tone. We hypothesized that the lowering of calcium and opening of potassium (K) channels as well as calciumindependent mechanisms are involved in H 2 S-induced relaxation in rat mesenteric small arteries. Amperometric recordings revealed that free [H 2 S] after addition to closed tubes of sodium hydrosulfide (NaHS), Na 2 S, and GYY4137 [P-(4-methoxyphenyl)-P-4-morpholinyl-phosphinodithioic acid] were, respectively, 14%, 17%, and 1% of added amount. The compounds caused equipotent relaxations in isometric myographs, but based on the measured free [H 2 S], GYY4137 caused more relaxation in relation to released free H 2 S than NaHS and Na 2 S in rat mesenteric small arteries. Simultaneous measurements of [H 2 S] and tension showed that 15 mM of free H 2 S caused 61% relaxation in superior mesenteric arteries. Simultaneous measurements of smooth muscle calcium and tension revealed that NaHS lowered calcium and caused relaxation of NE-contracted arteries, while high extracellular potassium reduced NaHS relaxation without corresponding calcium changes. In NE-contracted arteries, NaHS (1 mM) lowered the phosphorylation of myosin light chain, while phosphorylation of myosin phosphatase target subunit 1 remained unchanged. Protein kinase A and G, inhibitors of guanylate cyclase, failed to reduce NaHS relaxation, whereas blockers of voltage-gated K V 7 channels inhibited NaHS relaxation, and blockers of mitochondrial complex I and III abolished NaHS relaxation. Our findings suggest that low micromolar concentrations of free H 2 S open K channels followed by lowering of smooth muscle calcium, and by another mechanism involving mitochondrial complex I and III leads to uncoupling of force, and hence vasodilation.

No abstract

A 68-year-old man was admitted to hospital in an acute confusional state with a 2-week history of fever, influenza-like illness and sore throat. He quickly developed coagulation disturbances, hypotension and renal function impairment. Despite broad-spectrum antibiotic therapy, he deteriorated. Group A streptococcus (GAS) was recovered from blood cultures, which gave the diagnosis streptococcal toxic shock syndrome (STSS). A computed tomography scan showed a right-sided peritonsillar abscess (PTA). Acute tonsillectomy was carried out and the patient recovered. STSS complicating PTA has not previously been described in the literature, but GAS is a common pathogen in PTA. Clinicians should be aware that STSS can develop secondary to tonsillar infections and that abscess development should be suspected in STSS patients who do not respond to antibiotic treatment.