Hyperpolarization as a mechanism for endothelium‐dependent relaxations in the porcine coronary artery.

Abstract

SUMMARY1. The nature of endothelium-dependent relaxations resistant to nitro-L-arginine was investigated in porcine coronary arteries by measuring isometric force and membrane potential in the presence of indomethacin.2. Bradykinin induced concentration-and endothelium-dependent relaxations and hyperpolarization in tissues contracted with prostaglandin F2",. Nitro-L-arginine did not affect either the relaxations or the hyperpolarization induced by bradykinin. The threshold concentration of bradykinin was the same for the nitro-L-arginineresistant relaxations and the membrane hyperpolarization. 3. Nitro-L-arginine-resistant relaxations were evoked by several agents (A23187, thrombin and UK 14304) in addition to bradykinin. The amplitude of membrane hyperpolarizations observed with all agents was proportional to that of nitro-Larginine-resistant relaxations.4. Thrombin caused more transient relaxations and hyperpolarizations than bradykinin in the presence of nitro-L-arginine.5. In tissues contracted with high K+ or tetrabutylammonium (a non-selective K+-channel blocker), bradykinin inhibited the contractions in a concentrationdependent manner, whereas membrane hyperpolarization was not observed. The relaxations evoked by the kinin were abolished by nitro-L-arginine.6. These results suggest that endothelium-dependent relaxations which are resistant to nitro-L-arginine are mediated by membrane hyperpolarization in the porcine coronary artery.

Endothelial mediators of 17ß-estradiol-induced coronary vasodilation in the isolated rat heart

“…In addition, in the presence of L-NAME plus indomethacin or L-NAME plus clotrimazole, the response to 17ß-estradiol was significantly reduced in both groups, indicating the importance of PGI 2 and EDHF in the dilating response to 17ß-estradiol. Although NO/PGI 2 -independent agonist-induced vasodilatation is referred to as EDHF release (33), it is still unclear to what extent EDHF contributes to the vasodilating response when the synthesis of NO and PGI 2 is not inhibited. In our model of coronary microcirculation, the 17ß-estradiol-induced dilatation was attenuated by clotrimazole alone.…”

Antihypertensive Treatment Improves Endothelium-Dependent Hyperpolarization in the Mesenteric Artery of Spontaneously Hypertensive Rats

“…Hyperpolarization may induce relaxation in part by closure of voltage-dependent Ca 2ϩ channels. 8,10,37 Vascular tone has been shown to depend on voltage-dependent Ca 2ϩ influx to a greater extent in SHRs than in WKYs. 51 It follows that a given hyperpolarization might lead to greater relaxation in SHRs.…”

“…Also, EDHF-mediated hyperpolarization contributes to endothelium-dependent relaxation. 10,35,37 We previously showed that ACh-induced hyperpolarization and relaxation via EDHF are markedly impaired in the arteries of 6-to 8-month-old SHRs compared with age-matched WKYs. 10,25 Van de Voorde et al 24 reported an impairment of endothelium-dependent hyperpolarization in response to carbachol in the aortas of rats with renal hypertension.…”

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by NG‐nitro‐L‐arginine in pulmonary hypertension

“…Most endothelium-dependent vasodilators which release nitric oxide (NO, Moncada et al, 1991), also cause hyperpolarization of both endothelial and smooth muscle cells via opening of K+ channels (Beny et al, 1986;Nagao & Vanhoutte, 1992;Pacicca et al, 1992;Garland & McPherson, 1992;Eckman et al, 1994; for review, see Taylor & Weston, 1988). Studies by Cowan et al (1993) and Kilpatrick & Cocks (1994) indicate that although NO is the principal mediator of endothelialdependent relaxation in large systemic arteries, a K+ channeldependent mechanism acts as an important 'backup' for NO when its synthesis is blocked.…”