Strips Of Canine Coronary Arteries Research Articles

Effect of Ca2+/calmodulin-dependent protein kinase II inhibitors on the neurogenic cerebroarterial relaxation.

In canine cerebral artery strips contracted with prostaglandin F2alpha, transmural electrical stimulation (5 Hz for 40 s) produced a relaxation which was abolished by tetrodotoxin. The neurogenic response was inhibited moderately by [S]-5-isoquinolinesulfonic acid,4-[2-[(5-isoquinolinyl-sulfonyl)methylamino]-3-oxo-(4-phenyl-1-piperazinyl)-propyl] phenyl ester (KN62), an inhibitor of Ca2+ /calmodulin-dependent protein kinase II, which however did not alter or only slightly reduced the relaxant response to electrical nerve stimulation in canine coronary arterial strips that is mediated via beta-adrenoceptors stimulated by norepinephrine. Nicotine-induced relaxation, mediated by nitric oxide (NO) derived from perivascular nerves, was also attenuated by KN62, whereas the response to exogenous NO was unaffected. The nicotine-induced increase in the cyclic GMP content in cerebral arteries was depressed by KN62. The neurogenic relaxation was not influenced by phorbol 12-myristate 13-acetate, an activator of protein kinase C. 8-Bromo-cyclic GMP and 8-bromo-cyclic AMP did not significantly alter the response to nerve stimulation. It is concluded that the phosphorylation pathway involving Ca2+/calmodulin-dependent protein kinase II, but not other protein kinases so far tested, appears to be involved in the function of vasodilator nerves innervating the cerebral artery.

Effects of magnesium on isolated canine coronary arterial tension.

The effects of magnesium on the tension of isolated canine coronary arterial strips were studied. In the solution containing K+ of 20 mEq.l(-1), Ca2+ of 4 mEq.l(-1), and Na+ of 127 mEq.l(-1), the tension was 811 +/- 111 mg with Mg2+ of 1 mEq.l(-1), 494 +/- 135 mg with Mg2+ of 10 mEq.l(-1), 272 +/- 126 mg with Mg2+ of 20 mEq.l(-1), -52 +/- 63 mg with Mg2+ of 30 mEq.l(-1), -69 +/- 80 mg with Mg2+ of 40 mEq.l(-1). In the solution containing K+ of 20 mEq.l(-1), Na+ of 12 mEq.l(-1) and Ca2+ of 0 mEq.l(-1), the tension was 102 +/- 22 mg with Mg2+ of 1 mEq.l(-1), 3 +/- 35 mg with Mg2+ of 10 mEq.l(-1), -49 +/- 33 mg with Mg2+ of 20 mEq.l(-1), -59 +/- 49 mg with Mg2+ of 30 mEq.l(-1), -65 +/- 54 mg with Mg2+ of 40 mEq.l(-1). The data demonstrated that Mg2+ above 30 mEq.l(-1) inhibited the increase in tension caused by Ca2+ and Mg2+ above 20 mEq.l(-1) inhibited the increase in tension caused by low Na+ concentration.

Effects of calcium and temperature on tension in isolated canine coronary artery.

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied. In 20 mEq. l(-1) K solution, the tension was significantly increased from 0 mg with 0 mEq. l(-1) Ca to 33 +/- 18 mg with 0.2 mEq. l(-1) Ca at 37 degrees C, from -40 +/- 18 mg with 0 mEq. l(-1) Ca to -17 +/- 11 mg with 0.2 mEq. l(-1) Ca at 30 degrees C, from -77 +/- 19 mg with 0 mEq. l(-1) Ca to -52 +/- 17 mEq. l(-1) with 1 mEq. l(-1) Ca at 25 degrees C, from -88 +/- 13 mg with 0 mEq. l(-1) Ca to -41 +/- 18 mg with 2 mEq. l(-1) Ca at 20 degrees C, from -125 +/- 16 mg with 0 mEq. l(-1) Ca to -116 +/- 13 mg with 2 mEq. l(-1) Ca at 15 degrees C. Ca higher than 0.2 mEq. l(-1) produced a dose-dependent increase in tension between 37 degrees C and 15 degrees C. In spite of the presence of 4 mEq. l(-1) Ca, the development of tension was strongly supressed by lowering the temperature below 20 degrees C, and completely inhibited at 10 degrees C. The rate of a decrease in tension caused by cooling was about 5.5 mg. degrees C(-1). This study demonstrated that Ca(2+) produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.

Effects of sodium and temperature on tension in isolated canine coronary artery.

The effects of sodium and temperature on tension of isolated canine coronary arterial strips were studied. In 20 mEq. l(-1) K solution, the strength of tension was inversely related to the Na concentration. At 37 degrees C, the tension was significantly increased at 70 mEq. l(-1) Na and below. The tension was gradually suppressed by lowering of the temperature from 37 degrees C to 10 degrees C. At 10 degrees C, tension did not developed significantly at Na concentrations between 127 mEq. l(-1) and 12 mEq. l(-1). It was concluded that the decrease in Na concentrations increased the tension of the canine coronary artery and the lowering of temperature supressed the tension inducted by the decrease in Na concentrations.

Modification by severe hypoxia and diltiazem of dog coronary artery contractions in vitro

The contractions induced by prostaglandin (PG) F 2α and by Ca 2+ in helical strips of canine coronary arteries exposed to Ca 2+-free medium under severe hypoxia and stimulated by PGF 2α or K + were augmented by the return to normoxia. Inhibition under hypoxia was ranked as follows: Ca 2+-induced contractions in the strips stimulated by PGF 2 α > Ca 2+-induced contractions in the K +-depolarized strips `> PGF 2 α -induced contractions in the Ca 2+ -free medium. The inhibition of arterial contractions during severe hypoxia was not influenced by removal of the endothelium. Treatment with indomethacin attenuated the inhibitory effect of hypoxia on Ca 2+-induced contractions in arteries stimulated by PGF 2α or serotonin but affected neither the Ca 2+-induced contractions in the strips depolarized by excess K + or the PGF 2α-induced contractions in Ca 2+-free medium. Diltiazem attenuated the Ca 2+-induced contactions in arteries stimulated by PGF 2α or K ++ but did not attenuated the PGF 2α-induced contractions in the Ca 2+-free medium during hypoxia or normoxia. Diltiazem also inhibited the contractions caused by re-oxygenation. In conclusion, severe hypoxia inhibited the contractions induced by Ca 2+ in the presence of PGF 2α receptor activation more than those associated with membrane depolarization. The PGF 2α-induced contractions in the Ca 2+-free medium (possibly due to the release of intracellularly stored Ca 2+) may be relatively resistant to severe hypoxia. The hypoxia-induced inhibition of contractions due to Ca 2+ in PGF 2α-stimulated arteries could be associated partly with the release of PGI 2 but not with endothelium-derived relaxing factor(s).

Hypoxia releases a vasoconstrictor substance from the canine vascular endothelium.

Experiments were designed to determine the role of the endothelium in the facilitation by anoxia of contractile responses of isolated coronary arteries. Rings and strips of canine coronary arteries, with or without endothelium, were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution. To determine the release of a vasoactive substance(s) from the endothelial cells, strips without endothelium were layered with strips containing endothelium. In rings and in layered preparations with endothelium, anoxia (95% N2-5% CO2) augmented contractile responses to prostaglandin F2 alpha. Hypoxia (10 or 5% O2) caused contractions in the presence of indomethacin. Removal of the endothelium abolished the anoxic facilitation, and the hypoxic contractions. Inhibitors of cyclo-oxygenase, lipoxygenase or phospholipase A2 or of adrenergic, serotonergic and histaminergic receptors did not prevent the response to anoxia. Likewise, inhibitors of the endothelium-derived factor(s) (quinacrine, phenidone and methylene blue) did not affect the anoxic facilitation. Hypoxia and anoxia caused contraction of coronary arteries without endothelium when layered with femoral arteries and veins with endothelium. Anoxic facilitation was observed in femoral arteries, but not in femoral veins, with endothelium. These experiments indicate that hypoxia and anoxia cause the release of a diffusible vasoconstrictor substance(s) from endothelial cells. The sensitivity of smooth muscle of different anatomical origin to the facilitatory mediator(s) varies.

Hemolysate-induced release of prostaglandinlike substances from the canine cerebral arteries

The release of prostaglandinlike substances from canine pial arteries that was induced by exposure of the pial arteries to red blood cell hemolysate was estimated by using a superfusion technique for prostaglandin bioassay. The assay organs used were strips of rat stomach for prostaglandin E 2- or prostaglandin F 2α-like substances, strips of dog coronary artery for prostaglandin I 2-like substance, and strips of dog ileum for prostaglandin F 2α-like substance. The substances released from the canine pial arteries induced contractions in rat stomach strips and relaxations in canine coronary arterial strips, whereas they did not induce any response in canine ileal strips. The equivalent prostaglandin E 2 doses for the contractions of the rat stomach strips and the equivalent prostaglandin 1 2 doses for the relaxations of the canine coronary arterial strips were 125.2 ± 19.4 (n = 8) and 59.5 ± 16.4 (n = 6) pmol/g wet wt ± SEM, respectively.

Actions of bradykinin on isolated cerebral and peripheral arteries.

The addition of bradykinin (BK) caused a dose-related contraction in helical strips of canine cerebral, internal carotid, external carotid, and femoral arteries, while the peptide elicited a relaxation in canine coronary, renal, and mesenteric arteries contracted with 5+ or prostaglandin F2alpha. In contrast to canine cerebral arteries, human cerebral arteries contracted with K+ or prostaglandin relaxed with BK. Contractile responses of canine cerebral arteries to BK were not influenced by phentolamine, diphenhydramine, and methysergide, but were attenuated by aspirin and indomethacin. Contractions induced by K+ were not or only slightly inhibited by these anti-inflammatory agents. Polyphloretin phosphate failed to reduce BK-induced contractions. Relaxing effects of BK on canine coronary arterial strips were not altered by atropine, propranolol, metiamide, and aminophylline, but were inhibited by aspirin and indomethacin. Adenosine-induced relaxation was unaffected by the latter two agents. It may be concluded that adrenergic, cholinergic, histaminergic, and adenosine-related mechanisms are not involved in the genesis of BK-induced contraction and relaxation. Contractile responses of canine cerebral arteries to BK do not appear to derive from prostaglandins released, but rather from a direct action on vascular smooth muscle cells.