Hypertension in L-NAME-treated diabetic rats depends on an intact sympathetic nervous system.
We demonstrated previously that induction of diabetes in rats that were treated chronically with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) causes a severe, progressive increase in mean arterial pressure. This study tested the role of the sympathetic nervous system in that response. Rats were instrumented with chronic artery and vein catheters and assigned randomly to four diabetic groups pretreated with vehicle (D), L-NAME (D+L), the alpha(1)- and beta-adrenergic receptor antagonists terazosin and propranolol (D+B), or L-NAME, terazosin, and propranolol (D+LB). After baseline measurements were taken, rats were pretreated; 6 days later, streptozotocin was administered and 3 wk of diabetes ensued. D+L rats had a marked, progressive increase in arterial pressure that by day 20 was approximately 60 mmHg greater than in D rats. The pressor response to L-NAME was significantly attenuated in diabetic rats cotreated with adrenergic blockers. During week 1 of diabetes, plasma renin activity (PRA) increased and then returned to control levels in D rats. PRA increased progressively in D+L rats, and chronic adrenergic receptor blockade restored the biphasic renin response in D+LB rats. These results suggest that the sympathetic nervous system may be involved in the hypertensive response to onset of diabetes in L-NAME-treated rats, possibly through control of renin secretion.
Fitzgerald
Sharyn M
SM
Department of Physiology, Medical College of Georgia, Augusta, Georgia 30912-3000, USA.
Brands
Michael W
MW
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005919:Glomerular Filtration Rate; D006977:Hypertension, Renal / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D000804:Angiotensin II; D009569:Nitric Oxide; C041226:Terazosin; D012964:Sodium; D011433:Propranolol; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin