title: Genetic and dietary interactions: role of angiotensin AT1a receptors in response to a high-fructose diet.
abstract: The renin-angiotensin system (RAS) has been implicated in the cardiovascular complications of diabetes. We showed that a high-fructose diet increases blood pressure and plasma angiotensin and impairs glucose tolerance. We investigated the role of angiotensin AT(1a) receptors in the development of fructose-induced cardiovascular and metabolic dysfunction. Male angiotensin AT(1a) knockout (AT1aKO) and wild-type (AT1aWT) mice with arterial telemetric catheters were fed a standard diet or one containing 60% fructose. Fructose increased mean arterial pressure (MAP) in AT1aWT but only during the dark phase (8% increase). In AT1aKO mice, fructose unexpectedly decreased MAP, during both light and dark periods (24 and 13% decrease, respectively). Analytical methods were used to measure systolic arterial pressure (SAP) and pulse interval (PI) variability in time and frequency domains. In fructose-fed AT1aWT mice, there was an increase in SAP variance and its low-frequency (LF) domain (11 +/- 3 vs. 23 +/- 4 mmHg(2), variance, and 7 +/- 2 vs. 17 +/- 3 mmHg(2), LF, control vs. fructose, P < 0.004). There were no changes in SAP variance in AT1aKO mice. Depressor responses to alpha(1)-adrenergic blockade were augmented in fructose-fed AT1a WT compared with AT1aKO mice. Fructose inhibited glucose tolerance with a greater effect in AT1aWT mice. Fructose increased plasma cholesterol in both groups (P < 0.01) and reduced ANG II in AT1aKO mice. Results document prominent interactions between genetics and diet with data showing that in the absence of angiotensin AT(1a) receptors, a fructose diet decreased blood pressure.
authors: Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Colonel Glenn Hwy, Dayton, OH 45435, USA.
authors: Vera
authors: V
authors: Farah
authors: Khalid M
authors: KM
authors: Elased
authors: Mariana
authors: M
authors: Morris
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002940:Circadian Rhythm; D004040:Dietary Carbohydrates; D004195:Disease Models, Animal; D005632:Fructose; D018149:Glucose Intolerance / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006339:Heart Rate; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007333:Insulin Resistance / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011224:Prazosin / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D004040:Dietary Carbohydrates; D008055:Lipids; D044140:Receptor, Angiotensin, Type 1; D018340:Receptors, Adrenergic, alpha-1; D000804:Angiotensin II; D005632:Fructose; D011224:Prazosin