Cardiac anaphylaxis and the effects of glucagon pretreatment were studied in guinea‐pig isolated hearts actively sensitized to ovalbumin. Antigen challenge of the sensitized hearts markedly increased creatine Phosphokinase (CPK) activity in the coronary venous effluent. Control values of CPK release from the hearts before challenge were 3.56 ± 0.15 mu min−1 mg−1. In the first 10 min following challenge, CPK release remained stable at increased levels which ranged between 4.88 ± 0.20 to 5.39 ± 0.38 mu min−1 mg−1. There was no correlation between immunologically released histamine and CPK release. Pretreatment of the hearts with glucagon (0.15 μmol l−1) exerted a pronounced anti‐arrhythmic activity, reducing the conduction arrhythmias and completely preventing automaticity arrhythmias which normally occurred following ovalbumin challenge. Anaphylactic histamine release was reduced significantly in the presence of glucagon. The percentage inhibition of histamine release from glucagon pretreated hearts, during the first 10 min after challenge, ranged between 58% and 94% of that from hearts similarly challenged in the absence of glucagon. Glucagon significantly elevated sinoatrial nodal automaticity, enhanced atrioventricular conduction, improved coronary flow and reduced contractile force during anaphylaxis. It appears that these effects are caused both by modulating anaphylactic histamine release and by influencing the effects of the released histamine. CPK release from the anaphylactic hearts was significantly inhibited in the presence of glucagon. The average percentage inhibition of CPK activity during the first 10 min after challenge ranged between 42% and 98%. The findings from this study provide experimental evidence for protective effects of glucagon pretreatment during cardiac anaphylaxis.

The possible involvement of different effector systems (nitric oxide synthase, guanylate cyclase, β-adrenergic and muscarinic cholinergic receptors, cyclooxygenase and lipoxygenase, and Na+,K+-ATPase) was evaluated in a histamine H3 receptor agonist-induced ((R)α-methylhistamine, (R)α-MeHA) endothelium-dependent rat aorta relaxation assay. (R)α-MeHA (0.1 nM – 0.01 mM) relaxed endothelium-dependent rat aorta, with a pD2 value of 8.22 ± 0.06, compared with a pD2 value of 7.98 ± 0.02 caused by histamine (50% and 70% relaxation, respectively). The effect of (R)α-MeHA (0.1 nM – 0.01 mM) was competitively antagonized by thioperamide (1, 10 and 30 nM) (pA2 = 9.21 ± 0.40; slope = 1.03 ± 0.35) but it was unaffected by pyrilamine (100 nM), cimetidine (1 μM), atropine (10 μM), propranolol (1 μM), indomethacin (10 μM) or nordthydroguaiaretic acid (0.1 mM). Inhibitors of nitric oxide synthase, L-NG-monomethylarginine (L-NMMA, 10 μM) and NG-nitro-L-arginine methylester (L-NOARG, 10 μM) inhibited the relaxation effect of (R)α-MeHA, by approximately 52% and 70%, respectively). This inhibitory effect of L-NMMA was partially reversed by L-arginine (10 μM). Methylene blue (10 μM) and ouabain (10 μM) inhibited relaxation (R)α-MeHA-induced by approximately 50% and 90%, respectively. The products of cyclooxygenase and lipoxygenase are not involved in (R)α-MeHA-induced endothelium-dependent rat aorta relaxation nor are the muscarinic cholinergic and β-adrenergic receptors. The results also suggest the involvement of NO synthase, guanylate cyclase and Na+,K+-ATPase in (R)α-MeHA-induced endothelium-dependent rat aorta relaxation.

Thyroid hormones are the iodized derivatives of the amino acid tyrosine and are synthesized by the thyroid gland. Thyroxine (T 4 ) and triiodothyronine (T 3 ) regulate the processes of general metabolism (oxidative phosphorylation), growth, development and specific gene expression (Oppenheimer & Schwartz, 1987;Samuels, 1988). About 90 % of the thyroid production is T 4 while 10 % is T 3 . It is thought that T 4 has little, if any, biological activity, and it is considered as a prohormone, which becomes activated upon conversion into T 3 in peripheral tissues. About 80 % of the daily T 3 production is generated via this process while the remaining 20 % is directly secreted from the thyroid (Hennemann, 1987).To respond to thyroid hormone signals, cells have to contain specific thyroid hormone receptors (nuclear proteins) and thyroid hormone response elements (TRE) (specific DNA sequences upstream of regulated genes) (Brent et al. 1989). Thyroid hormone exerts its actions at a cellular level by binding to specific thyroid hormone receptor (TR) and binding of TR to TRE, in order to stimulate or inhibit the rate of transcription of specific genes (Franklyn & Gammage, 1996). Up to now, two major classes of thyroid hormone nuclear receptors have been described: thyroid hormone receptor-a (TRa) and thyroid hormone receptor-b (TRb) (Franklyn & Gammage, 1996;Nagaya et al. 1996). Several isoforms (a 1 , a 2 , a 3 , b 1 and b 2 ) are created by alternative splicing of TRa and TRb gene (Nagaya et al. 1996) and they display differences in terms of their tissue distribution and functional properties (Franklyn & Gammage, 1996). It has been shown that TRa 1 , TRa 2 and TRb 1 are expressed in the myocardium, and that TRa 1 and TRb 1 bind the ligand (thyroid hormone), while TRa 2 is non-ligand binding variant which may exert a 'dominant negative' influence on the action of a 1 and b 1 thyroid hormone receptor proteins (Brent et al. 1991;Franklyn & Gammage, 1996).Thyroid hormones have strong effects on the heart and circulation. It is considered that thyroid hormones perform direct and indirect actions on the heart. Thus, direct thyroid hormone actions on the heart involve regulation of transcription of a number of functionally relevant genes in the myocardium (nuclear mechanism). These include the myosin heavy chain contractile proteins (Ojamaa & Klein, 1993; Dubus et al. 1993), Na + ,K + -ATPase (Liu et al. 1993;Huang et al. 1994), Ca 2+ -ATPase and phospholamban (Kimura et al. 1994), which modulate the activity of calcium translocator (Klein & Ojamaa, 1996). But some effects, like the thyroid hormone effects on calcium uptake by the myocyte, are mediated by direct action on the plasma The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of 125 Kinetics of thyroxine (T 4 ) and triiodothyronine (T 3 ) transport in the isolated rat heart

The presence of histamine H3 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 Emax indicating competitive antagonism by pyrilamine (pA2 = 9.33 ± 0.34, slope = 1.09 ± 0.36) or thioperamide (pA2 =9.31 ± 0.16, slope=0.94 ± 0.10). Cimetidine (1 μM) 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)α-MeHA-induced (0.1 nM − 0.01 mM) endothelium-dependent relaxation was shifted to the right without significant change of Emax indicated competitive antagonism by thioperamide (pA2 = 9.21 ± 0.4, slope = 1.03 ± 0.35). Pyrilamine (100 nM) or cimetidine (1 μM) did not influence (R)α-MeHA-induced endothelium-dependent rat aorta relaxation. These results suggest the presence of a heterogenous population of histamine receptors, H1 and H3, on rat aorta endothelium.