Imidazoline receptors and agmatine in blood vessels: a novel system inhibiting vascular smooth muscle proliferation

S Regunathan, C Youngson, W Raasch, H Wang, D J Reis


We investigated whether vascular smooth muscle and endothelial cells express imidazoline (I-) receptors, their endogenous ligand agmatine and/or its biosynthetic enzyme arginine decarboxylase (ADC), and if I-receptors regulate smooth muscle proliferation. Membranes of cultured rat aortic smooth muscle or bovine pulmonary artery endothelial cells bind 3H-idazoxan. Binding was inhibited by: idazoxan > cirazoline > UK 14,304 > naphazoline > tolazoline > guanabenz > amiloride > clonidine = phentolamine > > epinephrine. Agmatine competitively inhibited binding of 3H-idazoxan (Ki of 240 +/- 25 nM). Smooth muscle and endothelial cells were immunostained in vitro and in situ by antibodies to an I-receptor binding protein and by antibodies to agmatine. Rat aorta also contained substantial amounts of agmatine measured by HPLC (8.69 +/- 1.1 ng/g). Membranes of rat aorta and cultured endothelial but not smooth muscle cells expressed substantial amounts of ADC. The incorporation of 3H-thymidine and numbers of smooth muscle cells stimulated by fetal calf serum was inhibited > 90% by: idazoxan > UK 14,304 > naphazoline > cirazoline > agmatine highly correlating (r= .996; P < .01) with affinities for 3H-idazoxan binding site. Tolazoline, but not rauwolscine, blocked the antiproliferative action of idazoxan. We conclude that (1) vascular smooth muscle and endothelium contain imidazoline receptors of the I2 subclass; (2) stimulation of the receptors inhibits vascular smooth muscle proliferation; (3) agmatine, synthesized in endothelium by ADC may be an endogenous agonist of I2 receptors to inhibit vascular growth and (4) I2 receptors may be functionally active.

Original languageEnglish
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number3
Pages (from-to)1272-82
Number of pages11
Publication statusPublished - 1996


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