The effects of phentolamine on fructose-fed rats.
Metabolic syndrome (MS) is a combination of medical disorders that increase the risk of developing cardiovascular disease and diabetes. MS is associated with obesity, increased blood pressure, hyperlipidemia, and hyperglycemia. This study was designed to investigate the pharmacological profile of phentolamine, a nonselective α adrenergic receptor antagonist, in the prevention of increased blood pressure in fructose-fed rats. Phentolamine prevented the fructose-induced increase in systolic blood pressure without affecting insulin sensitivity and major metabolic parameters. The levels of plasma noradrenaline and angiotensin II, 2 proposed contributors to the development of fructose-induced elevated blood pressure, were examined. Neither noradrenaline nor angiotensin II levels were affected by phentolamine treatment. Since overproduction of nitric oxide has been shown to lead to an elevation in peroxynitrite, the role of oxidative stress, a proposed mechanism of fructose-induced elevated blood pressure and insulin resistance, was examined by measuring plasma levels of total nitrate/nitrite. Plasma nitrate/nitrite was significantly elevated in all fructose-fed animals, regardless of treatment with phentolamine. Another proposed contributor toward fructose-induced MS is an elevation in uric acid levels. In this experiment, plasma levels of uric acid were found to be increased by dietary fructose and were unaffected by phentolamine treatment.
The University of British Columbia, Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada.
Kangbin
K
Zhou
Ujendra
U
Kumar
Violet G
VG
Yuen
John H
JH
McNeill
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005632:Fructose; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood; D010646:Phentolamine / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000097:blood; D014527:Uric Acid / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007328:Insulin; D026361:Reactive Nitrogen Species; D000804:Angiotensin II; D014527:Uric Acid; D005632:Fructose; D009638:Norepinephrine; D010646:Phentolamine