Effects of angiotensin II receptor antagonist on impaired endothelium-dependent and endothelium-independent relaxations in type II diabetic rats.

Abstract

BACKGROUND:

Diabetes mellitus is an important risk factor for cardiovascular diseases, and vasodilator dysfunction may contribute to vascular complications in diabetes. We previously demonstrated that the angiotensin II receptor blocker (ARB) corrected the impaired endothelium-derived hyperpolarizing factor (EDHF)-mediated arterial hyperpolarization and relaxation associated with hypertension or aging, partially independently of blood pressure.

OBJECTIVE:

To test whether EDHF-mediated, as well as endothelium-independent, relaxations would be altered in arteries from type II diabetic Goto-Kakizaki rats, and whether ARB would correct these alterations.

METHODS:

Goto-Kakizaki rats were treated with either the ARB candesartan or a combination of hydralazine and hydrochlorothiazide for 8 weeks, beginning at 10 weeks of age. Membrane potentials and contractile responses were recorded from the isolated mesenteric arteries.

RESULTS:

The two treatments lowered blood pressure comparably. Acetylcholine-induced, EDHF-mediated hyperpolarization and relaxation in mesenteric arteries were markedly impaired in untreated Goto-Kakizaki rats compared with age-matched Wistar rats, and neither ARB nor the combination therapy improved these responses. On the other hand, relaxations to endothelium-derived nitric oxide, assessed in rings precontracted with high potassium solution, were similar among the four groups. Relaxation to the nitric oxide donor sodium nitroprusside and that to levcromakalim, an ATP-sensitive K-channel opener, were also impaired in untreated Goto-Kakizaki rats, and the response to sodium nitroprusside was partially improved in treated Goto-Kakizaki rats.

CONCLUSIONS:

These findings suggest that EDHF-mediated hyperpolarization and relaxation and endothelium-independent relaxations are both impaired in arteries of type II diabetic rats, and antihypertensive treatment with or without ARB partially corrects endothelium-independent relaxations to the nitric oxide donor but not EDHF-mediated responses.

• Authors: Hideyuki Oniki, Koji Fujii, Yasuo Kansui, Kenichi Goto, Mitsuo Iida
• Journal: Journal of hypertension (J Hypertens) Vol. 24 Issue 2 Pg. 331-8 (Feb 2006) ISSN: 0263-6352 [Print] England
• PMID: 16508581 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Biological Factors
• Blood Glucose
• endothelium-dependent hyperpolarization factor

Topics

• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Biological Factors (physiology)
• Blood Glucose (analysis)
• Diabetes Mellitus, Type 2 (physiopathology)
• Endothelium, Vascular (physiology)
• Heart Rate
• Membrane Potentials
• Rats
• Rats, Wistar
• Systole
• Vasodilation (drug effects)