Hypertension and insulin resistance are not directly related in obese dogs.
In dogs fed a high-fat diet, we determined whether there was a direct relation between obesity-induced insulin resistance and obesity-induced hypertension. Thirty-six adult mongrel dogs were chronically instrumented and assigned to receive either a high-fat diet alone (n=7) or a high-fat diet combined with a low-sodium diet plus furosemide (n=6), prazosin plus atenolol (n=7), clonidine (n=10), or aspirin (n=6). Blood pressure, heart rate, and body weight were measured daily. Insulin resistance was assessed with a single-dose euglycemic hyperinsulinemic clamp (2 mU x kg(-1) x min(-1)) before and after 1, 3, and 6 weeks of the high-fat diet. The low-salt diet plus furosemide, prazosin plus atenolol, and clonidine treatments prevented the hypertension associated with feeding the dogs a high-fat diet. Only clonidine treatment totally prevented the development of insulin resistance, and high-dose aspirin, known to prevent insulin resistance by inhibition of the activity of IkappaB kinase-beta, decreased the degree of insulin resistance by almost 70%. However, aspirin had no effect on the development of hypertension. We conclude that obesity-induced hypertension and obesity-induced insulin resistance are not directly related. In addition, there is a suggestion that insulin resistance in this experimental model is mediated through the central and or peripheral alpha2-adrenoceptors, whereas hypertension is mediated through the alpha1- and or beta-adrenoceptors.
Division of Pediatric Cardiology, University of Michigan, Ann Arbor, USA. rocchini@umich.edu
Albert P
AP
Rocchini
John Q
JQ
Yang
Amy
A
Gokee
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D001262:Atenolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001786:Blood Glucose / Q000032:analysis; D003000:Clonidine / Q000494:pharmacology / Q000627:therapeutic use; D004039:Diet, Sodium-Restricted; D004041:Dietary Fats / Q000633:toxicity; D004285:Dogs; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D051550:I-kappa B Kinase; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D023421:Models, Animal; D008954:Models, Biological; D009765:Obesity / Q000150:complications* / Q000209:etiology; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000502:physiology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D001262:Atenolol; D005665:Furosemide; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; D003000:Clonidine; D001241:Aspirin; D011224:Prazosin