Histamine receptors on human isolated pulmonary arterial muscle preparations: effects of endothelial cell removal and nitric oxide inhibitors.
Human isolated intact pulmonary arterial muscle ring preparations which were precontracted with serotonin (10 microM) relaxed when stimulated with low concentrations of histamine, 2-[2-thiazolyl]ethylamine or 2-[pyridyl]ethylamine (pD2 values: 8.66 +/- 0.22, 7.10 +/- 0.06 and 6.20 +/- 0.26, respectively) or contracted at higher concentrations of these agonists. This relaxant response was obliterated in endothelial denuded tissues. Chlorpheniramine (H1-antagonist; 0.25 and 2.5 microM) induced a small contractile response in the tissues at resting tone (0.08 +/- 0.03 g and 0.10 +/- 0.10 g, respectively). Chlorpheniramine also shifted the histamine relaxation curves to the right (pD2 values: control, 8.85 +/- 0.31; 0.25 microM, 6.90 +/- 0.41; and 2.5 microM, 5.58 +/- 0.30; N = 6). Dimaprit (H2-agonist) induced a small relaxation (20%) in both intact and denuded tissues. Treatment of the tissues with cimetidine (H2-antagonist; 50 microM), burimamide (H2/H3-antagonist; 10 microM) and impromidine (H2-agonist/H3-antagonist; 1 microM) did not alter histamine-induced relaxation or contraction. Indomethacin (1.7 microM) caused a small contraction in these tissues and significantly reduced the histamine relaxation. The nitric oxide inhibitors (L-NG-monoethyl-L-arginine, 30 and 300 microM; or L-NG-nitroarginine, 30 and 300 microM) induced a slight and variable contraction in the preparations. However, these inhibitors, only in the presence of indomethacin, inhibited the relaxant effects of histamine and potentiated the contractions induced by this amine. These data suggest that a dual endogenous vasodilatory mechanism is present in human isolated pulmonary arterial muscle preparations and that products of the cyclooxygenase and endothelium-derived relaxing factor-nitric oxide pathway may interact to regulate histamine stimulation of H1-receptors.
Ortiz
J L
JL
Departamento de Farmacologia, Facultad de Medicina, Universitat de Valencia, Spain.
Labat
C
C
Norel
X
X
Gorenne
I
I
Verley
J
J
Brink
C
C
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002049:Burimamide / Q000494:pharmacology; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D011651:Pulmonary Artery / Q000378:metabolism* / Q000502:physiology; D011968:Receptors, Histamine / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013890:Thiourea / Q000494:pharmacology; D019323:omega-N-Methylarginine
D011968:Receptors, Histamine; D013757:Tetraethylammonium Compounds; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D012701:Serotonin; D002744:Chlorpheniramine; D019789:Tetraethylammonium; D002927:Cimetidine; D006632:Histamine; D001120:Arginine; D013890:Thiourea; D002049:Burimamide; D007213:Indomethacin; D017259:Dimaprit