Role of sympathetic nervous system in experimental hypertension and diabetes mellitus.
An investigation has been made to elucidate the role of sympathetic nervous system (SNS) in the development of renal hypertension and hyperglycemia in rats and rhesus monkeys using 6-hydroxydopamine (6-OHDA). Development of renal hypertension was blocked in weanling rats (80%), demedullated adult rats with 6-OHDA (75%) but not in adult rats sympathectomised with 6-OHDA. Weanling rats treated with 6-OHDA did not have any detectable catecholamine stores when measured 60 days after treatment with 6-OHDA. Unlike the weanling rats the hearts of the adult rats showed significant refilling of catecholamines 60 days after 6-OHDA treatment. 6-OHDA treatment and adrenalectomy did not modify the development of streptozotocin (STZ) induced hyperglycemia and the hypoglycemic effect of tolbutamide and phenformin. Chemical sympathectomy with 6-OHDA did not show any glucose intolerance in rhesus monkeys or any effect or insulin release. Phentolamine (PHE) and oxprenolol (OXP) pretreatment had no effect on development and maintenance of hyperglycemia. Although there was no effect on the endogenous catecholamines stored in the heart and brain in the diabetic rats, there was a marked increase in the urinary excretion of norepinephrine (NE), epinephrine (E), 3-methoxy-4 hydroxy mandelic acid (VMA) and creatinine. The rate of disappearance of (3H)-NE from rat heart was higher when compared to age matched controls. Diabetic rats showed increase responsiveness to angiotensin II and developed hypertension faster when their renal arteries were clamped as compared to controls. It is concluded that the functional SNS is important in the development of renal hypertension in the rat. Further the SNS in the rats and rhesus monkeys does not play any significant role in the STZ induced hyperglycemia, glucose intolerance and insulin release.
National Institute of Pharmaceutical Education and Research, S.A.S. Nagar (Mohali), Punjab, India.
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D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood / Q000652:urine; D003404:Creatinine / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D005500:Follow-Up Studies; D006977:Hypertension, Renal / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D008253:Macaca mulatta; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010096:Oxprenolol / Q000633:toxicity; D010646:Phentolamine / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D013311:Streptozocin; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D014642:Vanilmandelic Acid / Q000652:urine
D002395:Catecholamines; D010096:Oxprenolol; D014642:Vanilmandelic Acid; D013311:Streptozocin; D016627:Oxidopamine; D003404:Creatinine; D010646:Phentolamine