Endothelium‐derived relaxing, contracting and hyperpolarizing factors of mesenteric arteries of hypertensive and normotensive rats

Abstract

1 Di erences in the acetylcholine (ACh)-induced endothelium-dependent relaxation and hyperpolarization of the mesenteric arteries of Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were studied. 2 Relaxation was impaired in preparations from SHRSP and tendency to reverse the relaxation was observed at high concentrations of ACh in these preparations. 3 Relaxation was partly blocked by N G -nitro-L-arginine (L-NOARG, 100 mM) and, in the presence of L-NOARG, tendency to reverse the relaxation was observed in response to higher concentrations of ACh, even in preparations from WKY. The relaxation remaining in the presence of L-NOARG was also smaller in preparations from SHRSP. 4 The tendency to reverse the relaxation observed at higher concentrations of ACh in preparations from SHRSP or WKY in the presence of L-NOARG were abolished by indomethacin (10 mM). 5 Elevating the K + concentration of the incubation medium decreased relaxation in the presence of both indomethacin and L-NOARG. 6 Relaxation in the presence of L-NOARG and indomethacin was reduced by the application of both apamin (5 mM) and charybdotoxin (0.1 mM). This suggests that the relaxation induced by ACh is brought about by both endothelium-derived relaxing factor (EDRF, nitric oxide (NO)) and hyperpolarizing factor (EDHF), which activates Ca 2+ -sensitive K + channels. 7 Electrophysiological measurement revealed that ACh induced endothelium-dependent hyperpolarization of the smooth muscle of both preparations in the presence of L-NOARG and indomethacin; the hyperpolarization being smaller in the preparation from SHRSP than that from WKY. 8 These results suggest that the release of both NO and EDHF is reduced in preparations from SHRSP. In addition, indomethacin-sensitive endothelium-derived contracting factor (EDCF) is released from both preparations; the release being increased in preparations from SHRSP.

Prostaglandin I 2 and Prostaglandin E 2 Modulate Human Intrarenal Artery Contractility Through Prostaglandin E2-EP4, Prostacyclin-IP, and Thromboxane A2-TP Receptors

“…Acetylcholine-mediated relaxation was observed in 75% of vessels. Because endothelium-derived hyperpolarization is responsible for acetylcholine-induced responses in NO-blocked, human renal interlobar arteries 22 and K + -depolarization attenuates the response to acetylcholine compared with agonists, 23 the present data may have underestimated the functional state of the endothelium and the relaxing effect of PGI 2 and prostacyclin because membrane potential is clamped in response to elevated K + . The relaxation induced by prostacyclin was blocked by an IP receptor antagonist; the response was independent of the functional state of the endothelium, and IP mRNA and protein were detected in intrarenal arteries.…”

Impaired Endothelial Alpha-2 Adrenergic Receptor- Mediated Vascular Relaxation in the Fructose-Fed Rat

“…Data are shown as mean SEM. experimental design (isometric, isobaric contractions) and the type of precontraction drugs that were used (norepinephrine, phenylephrine, 5-HT) (18)(19)(20)(21).…”

Novel Nitric Oxide Synthase–Dependent Mechanism of Vasorelaxation in Small Arteries From Hypertensive Rats

“…There was a loss of the K ϩ channel pathway in small arteries from hypertensive rats, which is consistent with previous reports in small mesenteric arteries in SHR and ANG rats. 10,[31][32][33][34][35] Studies that have assessed EDHF-and NOS-mediated dilation in mesenteric resistance arteries from hypertensive rats and mice report decreased NO and/or EDHF contributions to relaxation in mesenteric arteries. 12,[32][33][34][35] Although it is very difficult to compare these studies because of differences in experimental protocols and/or animal models, many of these studies observed an imbalance of the EDHF and/or NOS pathways in the vasodilator response.…”