title: Increased functional Na(+)-K+ pump activity in the vasculature of fructose-fed hyperinsulinemic and hypertensive rats.
abstract: We hypothesized that hyperinsulinemia may alter insulin's ability to stimulate vascular Na+/K(+)-ATPase pump activity and modulate changes in vascular responsiveness associated with hypertension. We measured potassium-induced relaxation as an indicator of Na+/K(+)-ATPase pump activity in isolated femoral arteries from fructose-fed (FF) hyperinsulinemic, Sprague-Dawley rats. FF rats had higher mean arterial blood pressures than did normal diet-fed (NF) rats (FF, 125 +/- 2.2, n = 20, vs. NF, 113.5 +/- 2.5 mmHg, n = 20, p < 0.05) and were hyperinsulinemic (FF, 64 +/- 4 vs. NF, 37 +/- 2, microU/ml insulin, p < 0.01). FF rats were more sensitive to KCl in the Na+/K+ pump bioassay (FF, 0.86 +/- 0.07, n = 21 vs. NF, 1.18 +/- 0.08, n = 17, p < 0.05, expressed as ED50 in mmol/l KCl). Exogenous insulin (100 mU/ml) increased Na+/K+ pump sensitivity in FF rats as compared with a boiled insulin control (insulin 45 +/- 6%, n = 11, vs. control, 11 +/- 7%, n = 13, p < 0.01, expressed as percent increase in sensitivity, i.e., ED50). There were no significant differences in Na+/K+ pump sensitivity between insulin and control responses in the NF animals (insulin 29 +/- 6%, n = 11, vs. control 46 +/- 5%, n = 10, NS). Dose-response curves were obtained in tail and femoral arteries from the same animals to norepinephrine and acetylcholine, basally and after exogenous insulin. FF vessels had reduced sensitivity to norepinephrine as compared with the NF group. Insulin increased sensitivity to acetylcholine-induced relaxations and increased AII-induced contractions in FF-rat vessels. These data suggest that in the FF rat insulin's influence on the vascular Na+/K+ pump is enhanced and may modulate the changes in vascular responsiveness seen in this model.
authors.affiliation: Division of Endocrinology, Department of Veterans Affairs Medical Center, Sepulveda, CA 91343, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Berger
authors.forename: B L
authors.initials: BL
authors.lastname: Ormsby
authors.forename: P
authors.initials: P
authors.lastname: Bunnag
authors.forename: M T
authors.initials: MT
authors.lastname: Hori
authors.forename: M L
authors.initials: ML
authors.lastname: Tuck
authors.forename: M S
authors.initials: MS
authors.lastname: Golub
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005263:Femoral Artery / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D005632:Fructose / Q000008:administration & dosage; D006801:Humans; D006946:Hyperinsulinism / Q000178:diet therapy / Q000201:enzymology* / Q000503:physiopathology; D006973:Hypertension / Q000178:diet therapy / Q000201:enzymology* / Q000503:physiopathology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013623:Tail / Q000098:blood supply; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007328:Insulin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D005632:Fructose; D000254:Sodium-Potassium-Exchanging ATPase; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine