Komori, Kimihiro

The effects of nitric oxide and acetylcholine (ACh) were investigated on the electrical and mechanical properties of vascular smooth muscle cells of the canine mesenteric artery. Isolated tissues with or without the endothelium were contracted with prostaglandin F2 alpha. Nitric oxide caused comparable concentration-dependent relaxations in rings with and without endothelium. ACh induced concentration-dependent relaxations only in arteries with endothelium. The relaxations to both nitric oxide and ACh were inhibited by methylene blue or oxyhemoglobin. Either in the presence or absence of prostaglandin F2 alpha, ACh caused transient hyperpolarization of the cell membrane of the vascular smooth muscle. The ACh-induced transient hyperpolarization was not observed after mechanical removal of the endothelial cells or after treatment with atropine. Nitric oxide (less than or equal to 8 X 10(-6) M) did not alter membrane potential, in either the presence or absence of the endothelium. The excitatory junction potentials generated by perivascular nerve stimulation were inhibited by ACh but not by nitric oxide. These results suggest that in the canine mesenteric artery 1) the endothelium-derived hyperpolarizing factor generated by ACh is not nitric oxide; 2) nitric oxide relaxes vascular smooth muscle by a direct effect; and 3) nitric oxide does not modify adrenergic neurotransmission.

Experiments were designed to compare the sensitivity of venous and arterial smooth muscle to endothelin and to determine whether contractions to the peptide could be inhibited by endothelium-derived relaxing factor and nitric oxide. Rings of canine left anterior descending coronary, femoral, and mesenteric arteries and femoral and saphenous veins with and without endothelium were suspended for measurement of isometric force. In the presence of indomethacin, phentolamine, and propranolol, endothelin initiated concentration-dependent increases in tension in all rings. The veins were more sensitive to the peptide than were the arteries. Endothelin depolarized the smooth muscle of the saphenous veins and mesenteric arteries; the threshold concentration for depolarization was approximately 100 times lower in the veins (10(-10) M) than in the arteries (10(-8) M). Removal of the endothelium enhanced the sensitivity only of venous smooth muscle to endothelin. However, stimulation of the endothelium in the arteries with either acetylcholine or the calcium ionophore A23187 rapidly inhibited the maximal tension developed to the peptide. Nitric oxide inhibited contractions to endothelin in arteries and veins without endothelium; the inhibition was greater in the arteries than in the veins. These results indicate that venous smooth muscle is more sensitive than arterial smooth muscle to endothelin. In both blood vessels, endothelium-derived relaxing factor(s) can inhibit contractions to the peptide.

The present study examined the protective role of the venous endothelium against aggregating platelets and its modulation by diet. Yorkshire pigs were fed a regular chow (control pigs), 2% high-cholesterol diet (for 10 weeks, cholesterol-fed pigs), and regular chow plus cod-liver oil (30 ml/day for 4 weeks, oil-fed pigs). Endothelium-dependent responses were examined in vitro in rings of femoral veins in the presence of the inhibitor of cyclooxygenase indomethacin. In control pigs, aggregating platelets, serotonin, and ADP caused endothelium-dependent relaxations. The platelet-induced relaxations were attenuated by methiothepin (a combined 5-HT1 and 5-HT2 serotonergic blocker) or apyrase (an ADPase and ATPase) and were abolished by the combination of the two agents. In quiescent rings, platelets caused contractions, which were reduced in the presence of endothelium; the contractions were prevented by ketanserin (a 5-HT2 serotonergic blocker) or methiothepin but not by R 68 070 (a thromboxane A2 receptor blocker) or dazoxiben (a thromboxane-synthetase blocker). In cholesterol-fed pigs, the platelet-induced relaxations were not altered, whereas in oil-fed pigs, the endothelium-dependent relaxations to platelets, serotonin, and ADP were augmented. Platelet-induced contractions were significantly reduced in rings with endothelium from oil-fed pigs, whereas the contractions were comparable in rings without endothelium among the three groups. Endothelium-dependent relaxations in response to the calcium ionophore A23187, direct relaxations in response to sodium nitroprusside, and direct contractions in response to potassium chloride were comparable among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)