Vascular Reactivity to Phenylephrine and Angiotensin II in Hypertensive Rats Associated with Insulin Resistance

Abstract

Previous reports suggest that when rats are fed a carbohydrate-enriched diet they develop hyperinsulinemia associated with elevated blood pressure. The purpose of this study was to assess the vascular reactivity of fructose-treated rats to various pressor agents. Male Sprague Dawley rats (n=24) were used for this study and were divided into two equal groups. One of the groups was fed normal rat chow and served as the control group, whereas the other group was fed a fructose-enriched diet for four weeks. Mean blood pressure was elevated in the fructose-treated rats at the end of the second week of fructose treatment and remained elevated for the remainder of the study. At the end of the second and fourth weeks of fructose treatment, six rats from each group were used to assess both in vivo and subsequently in vitro vascular reactivity to various pressor agents. The jugular vein and carotid artery were cannulated under anesthesia. Twenty four hours after recovery from surgery pressor responses to angiotensin II (AII) and phenylephrine (PE) were determined. Twenty four hours later rats were decapitated and the thoracic aorta was removed, cleaned of adhering fat and cut into ring segments for vascular reactivity studies. Tissues were suspended in muscle baths containing physiological saline solution and maintained at 37d`C.

Dose-response curves were generated in the aorta in response to potassium chloride (KCl), A11 and PE. At the end of the second week of fructose treatment pressor response to A11 was significantly increased in the fructose-treated rats compared to the controls whereas there was no significant difference in pressor response to PE. There was no significant difference in pressor response to A11 and PE between the two groups at the end of the fourth week of fructose treatment. In vitro contractile response of the aorta to A11 and PE were significantly greater in the fructose-fed rats compared to the controls at the end of the second week of fructose treatment; however, there was no change in the EC₅₀ between the two groups. At the end of the fourth week of fructose treatment, the contractile responses to AII and PE were similar in both groups, although the response to A11 tended to be lower in the fructose-fed rat. There was no significant difference in the contractile response to potassium chloride oor in acetylcholine-induced relaxation throughout the study. These results strongly suggest that hypertension in fructose-treated rats is associated with increased in vitor vascular reactivity to All and PE in the early stages of hypertension.

Key Words:

• insulin resistance
• vascular reactivity
• fructose-induced hypertension
• angiotensin II
• phenylephrine
• pressor response