Endothelium-dependent vascular responses in normotensive and hypertensive Dahl rats.

Abstract

SUMMARY Experiments were designed to study endothelium-dependent responses in salt-sensitive (DS) and salt-resistant Dahl rats (DR). The rats were fed a low sodium (0.1% NaCl) or high sodium (8% NaCl) diet for 8 weeks. Blood pressure in DS fed a high sodium diet was higher than that in the remaining animals. Aortic rings with and without endothelium were suspended for isometric tension recording. Acetylcholine, adenosine 5'-diphosphate, and thrombin induced endothelium-dependent relaxations that were significantly depressed in the aorta of DS fed a high sodium diet. The relaxations in response to sodium nitroprusside were only slightly, but significantly, depressed in DS fed a high sodium diet. Removal of the endothelium greatly enhanced the response to serotonin and norepinephrine. In rings with, but not without, endothelium taken from rats fed a high sodium diet, the tension developed in response to serotonin and norepinephrine was significantly greater than that in animals fed a low sodium diet. These experiments indicate that (1) endothelium-dependent relaxations to acetylcholine, adenosine 5'-diphosphate, and thrombin are depressed in hypertensive Dahl rats; (2) this effect probably reflects a decreased release of endothelium-derived relaxing factor(s), although structural changes might contribute; and (3) 4 Endothelium-dependent relaxations to acetylcholine are depressed in spontaneous hypertension, in aortic coarctation, and in mineralocorticoid hypertension of the rat. "7 No information is available on endothelium-dependent responses of blood vessels in salt-induced hypertension. Received April 28, 1986; accepted August 20, 1986. Dahl developed two strains of rats with different propensities toward hypertension if fed a high sodium diet: a salt-sensitive strain, which becomes hypertensive when fed a high sodium diet, and a salt-resistant strain, which does not.8 This model may have similarities with a subgroup of human hypertension in which sodium contributes to the development of high blood pressure. 9 The present study was designed to investigate whether endothelium-dependent vascular responses are altered in salt-induced hypertension of the rat. Materials and MethodsMale 6-week-old Dahl salt-sensitive (DS) and saltresistant rats (DR) weighing 257 ± 7 g were purchased from Brookhaven National Laboratories (Brookhaven, NY, USA). All rats were housed two to a cage and had free access to water. For 8 weeks both DS and DR were fed standard rat chow (Ralston-Purina, St. Louis, MO, USA) that contained either 8% NaCl or 0.1% NaCl. Four groups of rats were used in the study: DS fed 8% NaCl, DS fed 0.1% NaCl, DR fed 8% NaCl, and DR fed 0.1% NaCl. Systolic blood 157 Downloaded from http://ahajournals.org by on April 28, 2019

Specific supersensitivity of the mesenteric vascular bed of Dahl salt-sensitive rats.

“…Luscher et al 16 reported a decline in the responsiveness of the endothelial relaxing mechanisms of aortic rings in DS rats with established hypertension. That finding is consistent with morphological signs of endothelial damage in mesenteric arteries of DS rats with established hypertension.…”

“…To investigate that possibility, relaxations induced by acetylcholine 16 were investigated in the presence of infusion of norepinephrine to induce vasoconstriction. With the exception of the highest dose in the DR normal salt group, there were no differences in response to acetylcholine in the DS high salt group relative to any other group.…”

Indirect evidence for release of endothelium-derived relaxing factor in human forearm circulation in vivo. Blunted response in essential hypertension.

“…10,15,40 We have compared the vasodilator action of acetylcholine in normal subjects and in patients with uncomplicated essential hypertension. In the hypertensive group, the reduction in FVR in response to acetylcholine was significantly less pronounced than that of normotensive control subjects.…”

Nitric oxide influences blood flow distribution in renovascular hypertension.

“…7 In various models of hypertension, including two-kidney, one clip (2K1C) Goldblatt, 1 aortic coarctation, 14 Dahl salt-sensitive, 3 and deoxycorticosterone acetate-salt 1 hypertension as well as in genetically spontaneously hypertensive rats, 2 endothelium-dependent vascular relaxation in vitro is impaired but may be restored by reversing the hypertension. 1 These observations suggest that endothelial dysfunction associated with hypertension may be due to insufficient production of the intrinsic vasodilator endothelium-derived nitric oxide (EDNO).…”