title: Regulation of vascular type 1 angiotensin II receptor in hypertension and sodium loading: role of angiotensin II.
abstract: OBJECTIVE
  To test the hypotheses that a high sodium intake increases steady state messenger RNA levels of the type 1 angiotensin II receptor in the aorta and mesenteric resistance arteries, and that this increase is mediated by suppression of production of angiotensin II induced by a high sodium intake; and to test the hypotheses that angiotensin II administered at a pressor dose increases steady state messenger RNA levels of the angiotensin II type 1 receptor in the aorta and mesenteric resistance arteries, and that this increase is mediated by activation of angiotensin II type 1 receptors in these vessels.
  
  
  METHODS
  In experiment 1, male Wistar rats were divided into four groups and treated for 2 weeks with a (0.5%) normal sodium diet, a normal-sodium diet plus angiotensin II, a high (4%) sodium diet, or a high-sodium plus angiotensin II. We infused 25 ng/kg per min angiotensin II subcutaneously by using osmotic pumps. In experiment 2, male Wistar rats were divided into four groups and treated for 2 weeks with vehicle, 1 mg/kg per day losartan by oral gavage, 250 ng/kg per min angiotensin II by using an osmotic pump), and losartan plus angiotensin II. Angiotensin II type 1 messenger mRNA was measured with the use of quantitative reverse transcriptase-polymerase chain reaction in the presence of an angiotensin II type 1 receptor mutant complementary RNA as internal standard.
  
  
  RESULTS
  Results from experiment 1 show that body weight and systolic tail-cuff blood pressures did not differ among our four groups (P > 0.05). Angiotensin II type 1 messenger RNA levels of rats in high-salt diet group were 73% (aorta) and 171% (mesenteric resistance arteries) greater than those of rats in normal-salt diet group (P < 0.05). In contrast, angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries of rats in normal-salt diet plus angiotensin II and high-salt diet plus angiotensin II groups did not differ from those of rats in normal-salt diet group. Results from experiment 2 show that systolic blood pressures in rats treated with angiotensin II and with losartan plus angiotensin II were higher than those in rats administered vehicle (P < 0.05). Mean response of arterial pressure to bolus injection of angiotensin II was suppressed in losartan-treated rats compared with that in rats administered vehicle and in rats treated with losartan plus angiotensin II compared with that in rats treated with angiotensin II (P < 0.05). Angiotensin II type 1 messenger RNA levels were higher by 73% (in aorta) and 63% (in mesenteric resistance arteries) in rats treated with angiotensin II than they were in rats administered vehicle (P < 0.05), but not in both aorta and mesenteric resistance arteries in rats treated with losartan and losartan plus angiotensin II versus rats administered vehicle.
  
  
  CONCLUSIONS
  A high-salt diet increases angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries. This increase is completely suppressed by simultaneous nonpressor infusion of angiotensin II, suggesting that angiotensin II negatively regulates vascular angiotensin II type 1 messenger RNA in normotensive rats. Hypertension induced by pressor infusion of angiotensin II increases angiotensin II type 1 messenger RNA levels both in aorta and in mesenteric resistance arteries. This increase can be prevented by administration of losartan at a nondepressor dose, suggesting that angiotensin II positively regulates vascular angiotensin II type 1 messenger RNA via activation of the angiotensin II type 1 receptor during hypertension.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-1065, USA. dwang@utmb.edu
authors.forename: D H
authors.initials: DH
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Du
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000502:physiology*; D012982:Sodium, Dietary / Q000008:administration & dosage*
chemical_list: D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000804:Angiotensin II