Relaxing actions of corticotropin‐releasing factor on rat resistance arteries

Abstract

1Although it well established that corticotropin-releasing factor (CRF) injected i.v. can cause hypotension and vasodilatation, there is no in vitro evidence that CRF acts as a vasodilator. We have therefore tested the hypothesis that the hypotensive effect of i.v. CRF is due to a direct vasodilator action by carrying out experiments in vitro on rat resistance arteries (i.d. 150-300ILm). 2 Initial in vivo experiments confirmed that CRF (1.5 nmol kg'1) injected i.v. caused hypotension in rats, this being partially antagonized by the CRF analogue CRF9-41.3 For the in vitro experiments, vessels were taken from the mesenteric, cerebral and femoral vascular beds, and mounted as ring preparations in an isometric myograph. The vessels were pre-contracted with one of 3 agonists (prostaglandin F2,, arginine vasopressin or noradrenaline) or with a high-potassium solution (K+). 4 With maximal concentrations of the agonists, CRF caused relaxation of mesenteric and cerebral vessels with 10nM, and near complete relaxation with 100nM. Femoral vessels preconstricted with agonists and all vessels preconstricted with K+ were less affected by CRF. In the mesenteric vessels, with sub-maximal levels of pre-constriction, CRF caused substantial relaxation at 1 nM and could cause complete relaxation at 10nM. 5 The relaxant effect of CRF on contractions of mesenteric vessels was antagonized by 100nM CRF9-41. Neither tetraethyl ammonium (30mM) nor glibenclamide (31 M) antagonized the relaxant effect of CRF. 6 The relaxant effect of CRF on mesenteric small arteries was found to be unaffected by removal of the endothelium. 7 The results indicate that CRF causes an endothelial-independent vasodilatation of rat resistance arteries under in vitro conditions at concentrations which are consistent with this being an important cause of the hypotension observed with i.v. injection of CRF.

Expression of corticotrophin-releasing hormone receptor mRNA and protein in the human myometrium

“…Many studies have demonstrated that CRH can exert actions by binding to several different cells, including immune (lymphocytes, macrophages) (McGillis et al 1989, Webster et al 1990) and vascular (endothelium, vascular smooth muscle) (Lei et al 1993, Barker & Corder 1995 cells which are likely to be present in myometrial tissue in addition to the predominant cell-type, the myocyte. Here, we have used a previously characterised antibody (Castro et al 1996) specific for the CRH R1 receptor to demonstrate that the R1 mRNA expressed in human myometrium is translated into protein and that this protein is indeed located on uterine smooth muscle cells within the tissue.…”

The role of corticotropin-releasing factor and noradrenaline in stress-related responses, and the inter-relationships between the two systems

“…Interestingly, there appears to be a substantial peripheral component to the delayed activation of the locus coeruleus-noradrenergic neurons, because the electrophysiologic activation was sensitive to the peripherally acting ganglionic blocker, chlorisondamine, and the largely peripherally acting β-adrenoceptor blocker, timolol (Borsody and Weiss, 1996). This may reflect changes in blood pressure, and may indicate a role for CRF in regulating blood pressure (it is to be noted that CRF possesses vasodilatory properties on peripheral blood vessels: Lei et al, 1993).…”

Corticotropin-releasing factor receptor 2 is a tonic suppressor of vascularization

“…Actions of CRFR2 ligands have been shown to produce a multitude of effects involving the peripheral vasculature, including vasodilation and sustained hypotension (17,23,25,(31)(32)(33). Ucn administration elevates cardiac contractility in conscious animals (34) and inhibits heat-induced edema (35).…”