dinoprost 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

The responsiveness of both the in vitro dorsal pedal artery and in vitro saphenous vein to alpha-adrenergic agents and prostaglandin F2 alpha was evaluated at baseline (prior to the onset of rapid ventricular pacing), at 1 week of pacing (mild heart failure), and 4 weeks after pacing when there was recovery from congestive heart failure. Eleven dogs were paced at 250 beats/min for 1 week and 7 dogs were paced for 3 weeks at 250 beats/min and allowed to recover from pacing for a further 4 weeks. At 1 and 4 weeks of recovery, compared to control, the maximal responsiveness of the dorsal pedal artery to norepinephrine was increased from 5.7 +/- 0.9 to 12.9 +/- 3.3 and 18.6 +/- 1.0 g/mm2, respectively. A similar finding was observed in the saphenous vein. The response of the artery to the selective alpha 1-agonist, phenylephrine, was also enhanced at 1 week. Moreover, the response of the artery and vein to phenylephrine was enhanced further at 4 weeks of recovery. In contrast, the response to the selective alpha 2-agonist, BHT 920, remained unaltered at these time points compared to control. Oxymetazoline, an agent used to differentiate between alpha 1-subdivisions, produced a significantly higher maximal response at 4 weeks of recovery (18.4 +/- 1.6 g/mm2 for the artery and 27.7 +/- 2.6 g/mm2 for the vein) compared to control (8.2 +/- 0.5 g/mm2 for the artery and 10.3 +/- 0.8 g/mm2 for the vein). The artery also displayed lower EC50 values for norepinephrine and phenylephrine at 1 week (0.7 and 2.2 microM, respectively) and 4 weeks of recovery (0.9 and 3.1 microM, respectively) compared to control (6.0 and 9.0 microM, respectively). In contrast, the only significant decreases in EC50's in the vein were the norepinephrine and oxymetazoline at 1 week of pacing (0.2 and 0.06 microM, respectively) compared to control (1.5 and 0.09 microM, respectively). The maximal tension developed to PGF2 alpha was enhanced after 1 week of pacing in both vessels and persisted 4 weeks following the cessation of pacing. Compared with control, EC50 values for PGF2 alpha were decreased at 1 and 4 weeks of recovery. We conclude that differences exist in peripheral vascular reactivity to both alpha 1-adrenoceptor agents and PGF2 alpha at 1 week of pacing and 4 weeks of recovery from pacing. Furthermore, the subtle reactivity differences between the artery and vein reflect different populations of alpha 1-adrenoceptors possibly associated with different signal transduction processes.

Topics: Adrenergic alpha-Agonists; Animals; Arteries; Azepines; Cardiac Pacing, Artificial; Dinoprost; Dogs; Dose-Response Relationship, Drug; Foot; Heart Failure; In Vitro Techniques; Male; Muscle Relaxation; Norepinephrine; Oxymetazoline; Saphenous Vein

Experiments were performed to assess the effects of acute moderate cooling on postjunctional alpha 1- and alpha 2-adrenoceptors in isolated rings of tail arteries from male Sprague-Dawley rats. Rings were contracted with norepinephrine (NE; 10(-9) to 10(-4) M) alone or in the presence of prazosin (Pz; 3 x 10(-7) M) or rauwolscine (Rw; 10(-7) M). NE concentration-response curves were inhibited by alpha 1-blockade (Pz) but not significantly affected by alpha 2-blockade (Rw). In all rings, cooling caused an increase in the slope of the dose-response curve and a significant increase in the concentration of agonist required to evoke contractions, as assessed by that concentration of NE required to evoke a contraction equal to 10% of maximal (EC10). Cooling inhibited contractions evoked by the selective alpha 1-adrenergic agonist phenylephrine (PE) as assessed by EC10 but had no significant effect on the weak contractions elicited by the selective alpha 2-adrenergic agonist B-HT 920. Prior elevation of tone with either KCl or prostaglandin F2 alpha enhanced alpha 2-mediated contractions. These contractions were augmented by cooling, whereas those caused by either KCl or prostaglandin F2 alpha alone were not significantly affected. Our results suggest that alpha 2-adrenoceptor-mediated responses in this blood vessel are dependent on the level of preexisting tone and are potentiated by cooling.

Topics: Animals; Arteries; Azepines; Cold Temperature; Dinoprost; Male; Muscle Contraction; Muscle, Smooth, Vascular; Norepinephrine; Phenylephrine; Potassium Chloride; Prazosin; Rats; Rats, Inbred Strains; Receptors, Adrenergic, alpha; Tail

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

Nicorandil, a potent coronary vasorelaxant used in the treatment of angina, has differential effects on arteries and veins in vivo. To explain this phenomenon, experiments were designed to characterize the relaxant and inhibitory actions of this compound on canine isolated arteries and veins. Paired rings of canine coronary, femoral, and saphenous arteries and saphenous veins were suspended at optimal length for isometric tension recording in organ chambers containing physiologic salt solution at 37 degrees C and gassed with 95% O2-5% CO2. In certain experiments, one ring of each pair was denuded of the endothelium. Removal of the endothelium did not affect nicorandil-induced relaxations of contracted blood vessels. Nicorandil exerted a differential relaxant effect on arteries and veins contracted with KCl (order of potency: saphenous vein greater than coronary artery greater than femoral artery). No difference in sensitivity to nicorandil was observed in arteries and veins contracted with prostaglandin F2 alpha. Contractions of saphenous arteries and veins to norepinephrine (NE) were equally sensitive to the inhibitory action of nicorandil. However, contractions of saphenous veins induced by sympathetic nerve stimulation were more sensitive to nicorandil than were contractions of saphenous arteries. Furthermore, nicorandil did not affect contractions to phenylephrine in saphenous veins, although contractions to B-HT 920 were virtually abolished by the compound. Saphenous veins contracted with St 587 were more sensitive to the relaxant action of nicorandil than when contracted with phenylephrine. These results suggest that nicorandil inhibits preferentially contractions of canine arteries and veins mediated by alpha 2- rather than alpha 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenergic alpha-Agonists; Animals; Arteries; Azepines; Dinoprost; Dogs; Drug Interactions; Endothelium, Vascular; Female; In Vitro Techniques; Male; Muscle Contraction; Niacinamide; Nicorandil; Norepinephrine; Phenylephrine; Sympathetic Nervous System; Synaptic Transmission; Vasodilator Agents; Veins

An analysis of vasopressor responses elicited by alpha-adrenoreceptor agonists and KCl in a constant pressure saline perfused model of rat perfused hindquarters is presented. Using methoxamine (alpha 1), cirazoline (alpha 1), B-HT 920 (alpha 2) and St 587 (alpha 1) as alpha-adrenoreceptor agonists, and rauwolscine and prazosin as selective alpha 2- and alpha 1-adrenoreceptor antagonists, respectively, it is concluded that alpha-adrenoreceptor mediated vasoconstriction in this model is mediated by the alpha 1-subtype. Pretreatment of the animals with reserpine (i.p., at various doses and dose-regimens) or addition of angiotensin II (10(-9)-10(-6) M), PGF2 alpha(10(-8) & 5 X 10(-7) M) or KCl (2 & 4 X 10(-3) M), or changing [Mg2+] did not significantly affect the potency or intrinsic activity of the alpha-adrenoreceptor agonists studied. Experiments with the calcium entry blocking drugs gallopamil and nifedipine, or deletion of CaCl2 from the perfusion solution, did not reveal a contribution from the influx of extracellular calcium towards alpha 1-adrenoreceptor-mediated reduction of flow in RPH. KCl-induced vasoconstriction in RPH was found to be sensitive to the blockade of calcium entry by calcium entry blocking drugs, but not to alpha-adrenoreceptor-blocking drugs and calmodulin antagonist. It is concluded that the model described here is of potential value in the characterization of alpha-adrenoreceptor antagonists and calcium entry blocking drugs under in vitro conditions in resistance vessels of the rat.

Topics: Acid-Base Equilibrium; Adrenergic alpha-Agonists; Angiotensin II; Animals; Azepines; Blood Pressure; Calcium; Clonidine; Dinoprost; Gallopamil; Hindlimb; Male; Perfusion; Potassium Chloride; Prostaglandins F; Rats; Receptors, Adrenergic, alpha; Regional Blood Flow; Reserpine