The role of NO and rho kinase in contractions to serotonin in diabetic mice

Abstract

Contraction to serotonin (5HT) is increased and relaxation to acetylcholine (ACH) is reduced in arteries from leptin receptor diabetic mice (DB) mice compared to non‐diabetics (ND). To determine the magnitude of the nitric oxide (NO) and rho kinase components in the vascular dysfunction in DB mice, responses of aorta from ND and DB to 5HT, ACH and nitroprusside (SNP) were measured before and after inhibition of NO synthase with nitro‐L‐arginine (LNA, 10μM) and rho kinase with H1152 (1μM). In ND aorta, 5HT produced concentration dependent contractions that were reduced by H1152. Contractions of aorta from DB mice to 5HT were increased compared to ND and also inhibited by H1152. Although LNA increased contraction to 5HT in ND mice, the inhibition by H1152 was similar. LNA had no effect on the contractions of aorta from DB mice to 5HT or the inhibition by H1152. LNA reduced whereas H1152 increased the relaxation to ACH in ND mice. Relaxation of aorta from ND to ACH was not affected by H1152 in the presence of LNA. Relaxation to ACH in DB mice was reduced approximately 50% compared to ND and LNA and H1152 had no effect on the relaxation. H1152 had no effect on relaxation to the NO‐independent dilator SNP in aorta from ND. We conclude that inhibition of rho kinase only increases relaxation to ACH in the presence of NO. Although NO modulates contractions to 5HT, it does not appear to modulate rho kinase‐mediated contractions to 5HT in mouse aorta.