calcimycin and talipexole

Experiments were designed to determine whether a heterogeneity of endothelium-dependent relaxations in arteries from different vascular beds exists in experimental congestive heart failure (CHF) and to determine the mediators of those responses. CHF was produced in dogs by rapid ventricular pacing for 15 d. Rings of coronary, femoral, and renal arteries with and without endothelium from control and CHF dogs were suspended in organ chambers for measurement of isometric force. In arteries contracted with prostaglandin F2 alpha, endothelium-dependent relaxations to BHT 920 (an alpha 2-adrenergic agonist) were increased in coronary arteries from dogs with CHF (maximal relaxation: control -15 +/- 9% vs CHF -92 +/- 5%; n = 5-6; P < 0.05), with a modest enhancement in renal arteries. Relaxations to adenosine diphosphate and the calcium ionophore were unchanged. Relaxations to BHT 920 in CHF were reduced by NG monomethyl-L-arginine (L-NMMA) and pertussis toxin but not by indomethacin. These data suggest that endothelium-dependent relaxations are affected heterogeneously in CHF. The enhanced response to alpha 2-adrenergic agonists in the coronary artery is mediated by nitric oxide through a mechanism sensitive to inhibition by pertussis toxin. This selective increase in endothelium-dependent relaxations in the coronary artery may contribute to preserving coronary blood flow during CHF.

Topics: Acetylcholine; Adenosine Diphosphate; Animals; Arginine; Atrial Natriuretic Factor; Azepines; Blood Pressure; Calcimycin; Cardiac Output; Coronary Vessels; Dinoprost; Dogs; Endothelium, Vascular; Femoral Artery; Heart Failure; Hemodynamics; In Vitro Techniques; Indomethacin; Isometric Contraction; Muscle, Smooth, Vascular; Nitric Oxide; omega-N-Methylarginine; Pertussis Toxin; Reference Values; Renal Artery; Renin; Vascular Resistance; Virulence Factors, Bordetella

In arteries, analogues of L-arginine inhibit the synthesis of nitric oxide and thereby reduce endothelium-dependent relaxations. Experiments were designed to determine whether analogues of L-arginine affect endothelium-dependent responses in a systemic vein. Rings cut from canine femoral arteries and veins were suspended for the measurement of isometric force in organ chambers. In some rings, the endothelium was deliberately removed. All experiments were conducted in the presence of indomethacin (10(-5) M). NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) reduced significantly endothelium-dependent relaxations to acetylcholine, ADP, and thrombin in arteries but not in veins. In the veins, the alpha 2-adrenergic agonist BHT-920 caused contractions which were reduced in rings with endothelium. L-NMMA eliminated the difference in contraction between rings with and without endothelium in the veins. This effect was reversed by L- but not D-arginine (3 x 10(-4) M). N omega-nitro-L-arginine (10(-4) M) reduced endothelium-dependent relaxations to acetylcholine, thrombin, and the calcium ionophore A23187 in venous rings. However, it did not alter the contractions to BHT-920 in rings with or without endothelium. L-Canavanine did not alter endothelium-dependent relaxations in the veins. These results suggest that synthesis of nitric oxide is associated with stimulation of alpha 2-adrenergic, muscarinic, and thrombin receptors on venous endothelial cells. Furthermore, the analogues of L-arginine affect endothelium-dependent relaxations in canine veins differentially.

Topics: Acetylcholine; Adenosine Diphosphate; Adrenergic beta-Antagonists; Animals; Arginine; Azepines; Calcimycin; Dogs; Endothelium, Vascular; Female; Femoral Artery; Femoral Vein; In Vitro Techniques; Indomethacin; Isomerism; Male; Muscle Contraction; Muscle, Smooth, Vascular; Nitric Oxide; Norepinephrine; omega-N-Methylarginine; Thrombin

This study was undertaken to determine whether clinical methods for preservation and storage of hearts explanted for transplantation affect the responsiveness of coronary arteries to vasoactive agents. Porcine hearts were perfused with crystalloid or blood cardioplegic solution. Rings of coronary arteries were suspended in organ chambers for measurement of isometric force (1) immediately after perfusion and (2) after 5 hours' storage of the hearts at 4 degrees C in the same cardioplegic solution (n = 6 in each group). The maximal contraction of the smooth muscle to potassium chloride, 40 mmol/L, was reduced significantly after perfusion with crystalloid cardioplegic solution (10.8 +/- 1.2 gm) compared with blood cardioplegic solution (17.3 +/- 0.8 gm) and nonperfused coronary arteries (control group 16.9 +/- 1.8 gm). The sensitivity of the arteries with endothelium to the contractile effects of prostaglandin F2 alpha increased after perfusion with crystalloid cardioplegic solution (ED50, [-log mol/L] 5.8 +/- 0.04) compared with blood cardioplegic solution (5.3 +/- 0.02) and the control group (5.7 +/- 0.03). In addition, relaxations to the calcium ionophore A23187, bradykinin, and the alpha 2-agonist BHT-920, which depend on the presence of endothelial cells, were significantly reduced after perfusion with crystalloid compared with blood cardioplegic solution or the control group. The responsiveness of the endothelium and smooth muscle after 5 hours' cold storage was unaltered in the blood cardioplegia group, whereas storage resulted in functional recovery in the crystalloid cardioplegia group, with the result that all groups were comparable. These data suggest an immediate and reversible change in vascular function with crystalloid cardioplegia, which was not apparent with blood cardioplegia.

Topics: Animals; Azepines; Bicarbonates; Bradykinin; Calcimycin; Calcium Chloride; Cardioplegic Solutions; Coronary Vessels; Dinoprost; Endothelium, Vascular; Female; Magnesium; Muscle Contraction; Potassium Chloride; Sodium Chloride; Swine; Time Factors

The responses of isolated canine portal veins, in either transverse or longitudinal strip, to alpha-2 adrenoceptor agonists were examined. B-HT920, a selective alpha-2 adrenoceptor agonist, did not elicit an appreciable response in the transverse strips of the portal vein under resting tone (0.5 g/mm width). When the preparation was partially precontracted with phenylephrine, prostaglandin F2 alpha, KCl, Bay K 8644, acetylcholine, 5-hydroxytryptamine, histamine, or A23187, B-HT920 evoked concentration-dependent contractile responses (3 x 10(-9)-10(-6) M). Maximum contractions, which depended on the precontraction levels and the precontracting substances, ranged from 10-35% of those evoked by norepinephrine 10(-5) M. Similar precontraction-dependent contractile responses were obtained in the longitudinal strips. Concentration-response curves of B-HT920 in the transverse strips precontracted with prostaglandin F2 alpha were shifted by yohimbine to the right, but not by prazosin. Schild analysis yielded a slope of unity and a pA2 of 8.79. Clonidine also showed a similar precontraction-dependent contractile response. The lower part of the concentration-response curve of clonidine was shifted by yohimbine. These results may be explained by the presence of postsynaptic alpha-2 adrenoceptors in canine portal vein, which mediate a contractile response under certain conditions.

Topics: Adrenergic alpha-Agonists; Animals; Azepines; Calcimycin; Cats; Clonidine; Female; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Portal Vein; Prazosin; Yohimbine