Control of arterial pressure by angiotensin II and nitric oxide at the onset of diabetes.
We have reported that the induction of diabetes in N(omega)-nitro-L-orginine methyl ester (L-NAME)-infused rats causes significant hypertension that is associated with increased plasma renin activity. This study tested the role of angiotensin II (Ang II) by clamping it chronically at baseline levels. The clamp consisted of an intravenous infusion of enalapril (10 mg/kg/d), which decreased mean arterial pressure (MAP) by approximately 20 mm Hg after 3 days, and adding chronic Ang II at 4 ng/kg/min, which restored MAP to normal. Chronic L-NAME infusion increased MAP to 127 +/- 1 and 132 +/- 2 mm Hg in normal and clamped rats, respectively, and induction of diabetes (streptozotocin) increased MAP progressively in normal rats to 161 +/- 8 mm Hg by day 12, whereas MAP in the clamped rats decreased progressively to 98 +/- 5 mm Hg by day 12. In non-L-NAME rats, MAP averaged 95 +/- 1 and 91 +/- 1 mm Hg for normal and clamped groups, respectively, before diabetes, and MAP was 10 to 13 mm Hg lower in the clamped versus normal rats midway through the diabetic period. This suggests that Ang II is important for maintaining blood pressure at the onset of diabetes, possibly to compensate for renal volume losses. Angiotensin II also is required for the hypertension caused by induction of diabetes in rats with chronic blockade of nitric oxide synthesis, but whether this is due to increased volume sensitivity in L-NAME-treated, vasoconstricted rats remains to be determined.
Brands
Michael W
MW
Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912-3000, USA. mbrands@mcg.edu
Cloud
Leslie J
LJ
D000804:Angiotensin II / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000188:drug therapy; D003921:Diabetes Mellitus, Experimental; D004656:Enalapril / Q000494:pharmacology; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D008297:Male; D023421:Models, Animal; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D004656:Enalapril; D019331:NG-Nitroarginine Methyl Ester