Adrenomedullin-Induced Endothelium-Dependent Relaxation in Porcine Ciliary Arteries

Abstract

In isolated porcine ciliary arteries, adrenomedullin induces relaxation that involves CGRP(1) receptors and is in part endothelium dependent. Endothelium-dependent relaxation was blocked by some potassium channel inhibitors, suggesting the possible release of an endothelium-derived hyperpolarizing factor (EDHF).

Pharmacological characterisation of the mechanisms underlying the relaxant effect of adrenomedullin in the rat carotid artery

“…Vasodilator prostanoids mediates AM‐induced relaxation in rat pulmonary arteries[27] and porcine ciliary arteries [10]. This study shows that in the rat carotid, AM increased 6‐keto‐PGF 1α generation (stable metabolite of prostacyclin) and that AM‐induced relaxation was partially blunted by SC560, suggesting the involvement of vasodilator cyclooxygenase‐1 metabolite (probably prostacyclin) in the relaxing effect of AM.…”

“…In fact, the receptor mediating AM‐induced relaxation varies with the blood vessel studied. For example, the relaxation induced by AM was inhibited by CGRP 8–37 , a selective CGRP receptor antagonist, but not by AM 22–52 , a selective AM receptor antagonist, in rat mesenteric arteries,[8] mice aorta,[9] pig ciliary artery[10] and human coronary artery [11]. On the other hand, AM‐induced relaxation was inhibited by AM 22–52 but not CGRP 8–37 in the rat aorta [12,13].…”

“…In renal artery of dogs,[15] rat aorta[12] and bovine retinal artery,[14] the vasodilator effect of AM is endothelium‐dependent and mediated by nitric oxide (NO). However, it was observed that in human coronary artery[16] and suine ciliary arteries,[10] the opening of K + channels also play a role in the vasodilatation induced by AM. On the other hand, Ishizaka et al [17].…”

The discovery of the Flammer syndrome: a historical and personal perspective

“…We described the localisation of AT1- [119, 120], melatonin- [121] and melanin-concentrating hormone receptors [91] and characterised the influence of local anaesthetics [122]. Further studies explored the effect of ACE inhibitors and angiotensin receptor antagonists [123], of CCBs [124] at high and low doses [125], dipyridamole [126], potassium-channel blockers [127] and openers [128], magnesium [129], ox-LDL and the ET antagonists BQ 123 [130] and avosentan [131], bimatoprost [132], carteolol [133, 134], PGF2alpha [135] travoprost [136], latanoprost [137, 138], melatonin [139] and adrenomedullin [140]. We also studied the regulation of the vortex vein [101].…”

Adrenomedullin regulates intestinal physiology and pathophysiology

“…Adrenomedullin gene expression is upregulated in cardiovascular tissues of dogs with congestive heart failure due to mitral regurgitation [17], and with myxomatous mitral valvular disease [16]; in feline hearts with cardiomyopathy [13]; in lungs of pulmonary hypertensive chickens [18]; and in critically ill foals [19]. Adrenomedullin elicits a vasorelaxing effect in feline pulmonary arteries and veins [20], in bovine retinal arteries [21] and cerebral microvasculature [22], and in porcine ciliary and pulmonary arteries [23,24]. In chicks, AM seems to regulate food intake acting through hypothalamic pathways [25].…”