ABSTRACT
The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, beta-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na(+),K(+)-ATPase) was evaluated in a histamine H(3) receptor agonist-induced ((R)alpha-methylhistamine, (R)alpha-MeHA) endothelium-dependent rat aorta relaxation assay. (R)alpha-MeHA (0.1 nM - 0.01 mM) relaxed endothelium-dependent rat aorta, 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, respectively). 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 muM), atropine (10 muM), propranolol (1 muM), indomethacin (10 muM) or nordthydroguaiaretic acid (0.1 mM). Inhibitors of nitric oxide synthase, L-N(G)-monomethylarginine (L-NMMA, 10 muM) and N(G)-nitro-L-arginine methylester (L-NOARG, 10 muM) inhibited the relaxation effect of (R)alpha-MeHA, by approximately 52% and 70%, respectively). This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 muM). Methylene blue (10 muM) and ouabain (10 muM) 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 muscarinic cholinergic and beta-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na(+),K(+)-ATPase in (R)alpha-MeHA-induced endothelium-dependent rat aorta relaxation.
ABSTRACT
The presence of histamine H(3) receptors was evaluated on the rat aorta endothelium. In the presence of pyrilamine (1 nM, 7 nM, 10 nM) or thioperamide (1 nM, 10 nM, 30 nM) the concentration-response curve for histamine-induced (0.1 nM - 0.01 mM) endothelium-dependent rat aorta relaxation was shifted to the right without significant change of the E(max) indicating competitive antagonism by pyrilamine (pA(2) = 9.33 +/- 0.34, slope = 1.09 +/- 0.36) or thioperamide (pA(2) =9.31 +/- 0.16, slope=0.94 +/- 0.10). Cimetidine (1 muM) did not influence histamine-induced endothelium-dependent rat aorta relaxation. In the presence of thioperamide (1 nM, 10 nM, 30 nM) the concentration-response curve for (R)alpha-MeHA-induced (0.1 nM - 0.01 mM) endothelium-dependent relaxation was shifted to the right without significant change of E(max) indicated competitive antagonism by thioperamide (pA(2) = 9.21 +/- 0.4, slope = 1.03 +/- 0.35). Pyrilamine (100 nM) or cimetidine (1 muM) did not influence (R)alpha-MeHA-induced endothelium-dependent rat aorta relaxation. These results suggest the presence of a heterogenous population of histamine receptors, H(1) and H(3), on rat aorta endothelium.
ABSTRACT
Effect of glucagon on energy-metabolite transport into cardiac muscle was studied during a single transit through the isolated rabbit heart using a rapid paired-tracer dilution method. Kinetic experiments revealed that 1.5 microM glucagon stimulated the influx of palmitate bound to 30 g/litre albumin, by increasing the V 2.3 times and increasing the Km for transport 2.4 times. Tracer uptake of D-glucose, as the only exogenous substrate provided, was increased by 80% by 1.5 microM glucagon. Myocardial utilization of [3H]-or [14C]-labelled short-chain monocarboxylic acids (L-lactate, pyruvate and acetate) was significantly reduced by glucagon, to the same degree as their unidirectional sarcolemmal transport. Inhibition of L-[14C]lactate uptake was dose-dependent and in positive correlation with myocardial lactate production. It is concluded that glucagon may regulate sarcolemmal permeability and myocardial utilization for energy-metabolites from the coronary circulation.
