Published Online
on March 8, 2004

A more recent version of this article appeared on May 1, 2004

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Submitted on December 4, 2003
Revised on December 24, 2003

Hypertension and Insulin Resistance Are Not Directly Related in Obese Dogs

Albert P. Rocchini^*; John Q. Yang; and Amy Gokee

From the Division of Pediatric Cardiology, University of Michigan, Ann Arbor.

^* To whom correspondence should be addressed. E-mail: rocchini{at}umich.edu.

Abstract--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 · kg^-1 · 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 IB kinase-, 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 ₂-adrenoceptors, whereas hypertension is mediated through the ₁- and or -adrenoceptors.

Key words: hypertension • obesity • insulin resistance • sympathetic nervous system

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