ENDOTHELIUM-DEPENDENT RELAXATION OF RAT AORTA TO A HISTAMINE H-3 AGONIST IS REDUCED BY INHIBITORS OF NITRIC-OXIDE SYNTHASE, GUANYLATE-CYCLASE AND NA-ATPASE(,K+)

The possible involvement of different effector systems (nitric oxide s ynthase, guanylate cyclase, beta-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na+,K+-ATPase) was ev aluated in a histamine H-3 receptor agonist-induced ((R)alpha-methylhi stamine, (R)alpha-MeHA) endothelium-dependent rat aorta relaxation ass ay. (R)alpha-MeHA (0.1 nM-0.01 mM) relaxed endothelium-dependent rat a orta, with a pD(2) value of 8.22 +/- 0.06, compared with a pD(2) value of 7.98 +/- 0.02 caused by histamine (50% and 70% relaxation, respect ively). The effect of (R)alpha-MeHA (0.1 nM-0.01 mM) was competitively antagonized by thioperamide (1, 10 and 30 nM) (pA(2) = 9.21 +/- 0.40; slope = 1.03 +/- 0.35) but it was unaffected by pyrilamine (100 nM), cimetidine (1 mu M), atropine (10 mu M), propranolol (1 mu M), indomet hacin (10 mu M) or nordihydroguaiaretic acid (0.01 mM). Inhibitors of nitric oxide synthase, L-N-g-monomethylargine (L-NMMA, 10 mu M) and N- g-nitro-L-arginine methylester (L-NOARG, 10 mu M) inhibited the relaxa tion effect of (R)alpha-MeHA, by approximately 52% and 70%, respective ly). This inhibitory effect of L-NMMA was partially reversed by L-argi nine (10 mu M). Methylene blue (10 mu M) inhibited relaxation (R)alpha -MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (R)alpha-MeHA- induced endothelium-dependent rat aorta relaxation nor are the muscari nic cholinergic and beta-adrenergic receptors. The results also sugges t the involvement of NO synthase, guanylate cyclase and Na+, K+-ATPase in (R)alpha-MeHA-induced endothelium-dependent rat aorta relaxation.