Endothelin vascular receptors and responses in deoxycorticosterone acetate-salt hypertensive rats.

Abstract

The vasoconstrictor effect, the binding, and the response of inositol phosphates to endothelin-1 (ET-1) were investigated in blood vessels of deoxycorticosterone acetate (DOCA) -salt hypertensive rats within 2 weeks of development of hypertension and in uninephrectomized control rats. In DOCA-salt and uninephrectomized rats, plasma levels of endothelin were similar (1.2±0.1 fmol/ml). Thoracic aorta and mesenteric artery rings devoid of endothelium presented significantly decreased responses to increasing concentrations of ET-1. Binding of ET-1 to mesenteric artery membranes was significantly lower in DOCA-salt rats (106±22 fmol/mg protein) than in uninephrectomized rats (172 ±19 fmol/mg protein, p< 0.05), whereas affinity was similar. Phosphoinositide metabolism was examined in aorta and mesenteric arteries after incubation with The endothelium synthesizes and releases paracrine hormones that regulate the contraction and physiology of vascular smooth muscle cells. 4 In addition to the well-described vasorelaxant factors (i.e., endo-

Endothelin‐1‐induced contraction in isolated aortae from normotensive and DOCA‐salt hypertensive rats: effect of magnesium

“…These findings are in agreement with previous reports indicating that ryanodine inhibits contractions when agonist concentrations are low, whereas contractions elicited by high concentrations of the agonist are not affected (Kanmura et al, 1988). The finding that contractions induced by endothelin-1 are blunted in DOCA-salt hypertensive rats has been previously shown in aortae and mesenteric arteries Nguyen et al, 1992). Decreased endothelin-l binding Endothelin-1, log (M) Figure 4 Concentration-response curves to endothelin-I in isolated aortae from normotensive rats (a, c) and DOCA-salt hypertensive rats (b, d sites and decreased activation of phospholipase C, with decreased production of inositol phosphates may explain the blunted contraction in tissues from DOCA-salt hypertensive rats with 2-3 weeks of developing hypertension (Fukuda et al, 1988;Nguyen et al, 1992).…”

“…The finding that contractions induced by endothelin-1 are blunted in DOCA-salt hypertensive rats has been previously shown in aortae and mesenteric arteries Nguyen et al, 1992). Decreased endothelin-l binding Endothelin-1, log (M) Figure 4 Concentration-response curves to endothelin-I in isolated aortae from normotensive rats (a, c) and DOCA-salt hypertensive rats (b, d sites and decreased activation of phospholipase C, with decreased production of inositol phosphates may explain the blunted contraction in tissues from DOCA-salt hypertensive rats with 2-3 weeks of developing hypertension (Fukuda et al, 1988;Nguyen et al, 1992). In other studies, however, phosphoinositide breakdown has been shown to be enhanced in response to endothelin-1 in mesenteric arteries and atria from DOCA-salt hypertensive rats (De Champlain et al, 1989).…”

Increased expression of endothelin-1 gene in blood vessels of deoxycorticosterone acetate-salt hypertensive rats.

“…20 We have previously shown that in DOCA-salt hypertensive rats, responses of aorta and large and small mesenteric arteries to exogenous ET-1 are blunted. 7 - 21 Furthermore, binding of ET-1 to mesenteric arteries is decreased, and signal transduction is also blunted in both mesenteric arteries and aorta. 7 - 22 This suggests that, indeed as a consequence of increased production of ET-1 in blood vessels of DOCA-salt hypertensive rats, endothelin receptors are downregulated, resulting in depressed responses to exogenous and probably endogenous endothelin.…”

“…7 - 21 Furthermore, binding of ET-1 to mesenteric arteries is decreased, and signal transduction is also blunted in both mesenteric arteries and aorta. 7 - 22 This suggests that, indeed as a consequence of increased production of ET-1 in blood vessels of DOCA-salt hypertensive rats, endothelin receptors are downregulated, resulting in depressed responses to exogenous and probably endogenous endothelin. Because the walls of blood vessels in DOCA-salt rats are significantly hypertrophied and their lumen reduced, vasoconstrictor responses are magnified in resistance vessels, 21 and thus increased production of ET-1 may play a role in the maintenance of hypertension in this model despite depressed responsiveness to ET-1.…”

Calcium, phosphoinositide, and 1,2-diacylglycerol responses of blood vessels of deoxycorticosterone acetate-salt hypertensive rats to endothelin-1.

“…8 -9 In a previous study we reported that the density of mesenteric artery ET-1 receptors and vascular responses to ET-1 are decreased in DOCA-salt hypertensive rats. 3 Moreover, we demonstrated that vascular accumulation of inositol phosphates (InsPs) in response to ET-1 was significantly lower in DOCA-salt hypertensive rats when compared with uninephrectomized controls. These observations led to the question of whether diacylglycerol (DG) production and intracellular calcium metabolism are also altered in DOCA-salt hypertensive rats.…”