Identification of endothelial H1, vascular H2 and cardiac presynaptic H3 receptors in the pithed rat

Abstract

In pithed and vagotomized rats the effects of the H3 receptor agonist R-(-)-alpha-methylhistamine, the H1 receptor agonist 2-(2-thiazolyl)ethylamine and the H2 receptor agonist dimaprit on basal diastolic blood pressure, basal heart rate and the electrically induced rise in heart rate were examined. Basal diastolic blood pressure was not altered by low, but increased by high doses of R-(-)-alpha-methylhistamine; the latter effect was not affected by selective H1, H2 or H3 receptor antagonists and by prazosin, but was attenuated by rauwolscine. Rauwolscine also unmasked a vasodepressor response to R-(-)-alpha-methylhistamine not affected by the H3 receptor antagonist thioperamide, but counteracted by the H1 receptor antagonist dimetindene or the H2 receptor antagonist ranitidine. The vasodepressor responses to 2-(2-thiazolyl)ethylamine and dimaprit were antagonized by dimetindene and ranitidine, respectively. The vasodepressor response to 2-(2-thiazolyl)ethylamine was not altered by indomethacin, but reduced by an inhibitor of endothelial nitric oxide synthase, N omega-nitro-L-arginine methyl ester (which, by itself, markedly increased blood pressure). Both drug tools did not alter the effect of dimaprit. Basal heart rate was not affected by 2-(2-thiazolyl)ethylamine (examined after administration of propranolol), dimaprit and R-(-)-alpha-methylhistamine. The electrically induced increase in heart rate (studied in animals which had received rauwolscine) was decreased by R-(-)-alpha-methylhistamine but not affected by 2-(2-thiazolyl)ethylamine and dimaprit. The effect of R-(-)-alpha-methylhistamine was abolished by thioperamide. R-(-)-alpha-methylhistamine did not influence the increase in heart rate produced by isoprenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic GMP‐independent relaxation and hyperpolarization with acetylcholine in guinea‐pig coronary artery

“…The results suggest that basal cyclic GMP levels are almost exclusively due to spontaneous release of NO. The HI receptor agonist, AEP, was capable of eliciting contraction in the presence of these basal levels of cyclic GMP and interestingly, although HI receptors are also reported to be present on endothelial cells in some blood vessels (Chen & Suzuki, 1989;Malinowska & Schlicker, 1993) we did not observe a significant change in cyclic GMP levels when AEP was added to the tissue. Basal cyclic GMP levels appear to modulate contractions however, since significantly larger contractions were obtained in the presence of either L-NMMA or HbO.…”

(R)-Alpha-Methylhistamine Inhibits Ethanol-lnduced Gastric Lesions in the Rat: Involvement of Histamine H₃ Receptors?

“…while the electrically induced increases in blood pressure andin heart rate are inhibited at 0.01 -10 pmol/kg i.v. [ 14,15]. By comparing MHA dose ranges in our and other studies, it can be concluded that a high dose range is required to achieve protection of the gastric mucosa.…”

Mediation of the positive chronotropic effect of CGP 12177 and cyanopindolol in the pithed rat by atypical β‐adrenoceptors, different from β3‐adrenoceptors

“…Body temperature was kept constant at 37 + 1°C. Following pithing, blood pressure was routinely raised to 80-100 mmHg by infusion of vasopressin (0.04 -0.4 i.u., kg-1 min-') into the right femoral vein (since vasopressor/vasodepressor effects are more marked at a higher level of blood pressure; see, e.g., Malinowska & Schlicker, 1993). After 15-30 min of equilibration, during which the cardiovascular parameters were allowed to stabilize, experiments were performed.…”