A Reduction in the Amount and Anti-Contractile Effect of Periadventitial Mesenteric Adipose Tissue Precedes Hypertension Development in Spontaneously Hypertensive Rats

Abstract

The aim of this study was to determine whether alterations in periadventitial adipose tissue and its anti-contractile effect precede hypertension development. We used 4-week-old male Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), which were pre-hypertensive. Vascular function was studied in the perfused mesenteric bed (MB, 1.5 mL/min). MB weight was lower in SHR (8.0 +/- 0.3 mg/g body weight) than in WKY (9.0 +/- 0.3 mg/g body weight) rats. Concentration-response curves to KCI (6 to 75 mmol/L) and to acetylcholine (10(-9) to 10(-5) mol/L) were similar between groups. Contractile responses to serotonin (10(-9) to 10(-5) mol/L) were significantly higher in SHR compared to WKY. 4-Aminopyridine (4-AP, 2 mmol/L), a blocker of Kv channels, induced a similar increase in perfusion pressure in both strains. However, 4-AP (2 mmol/L) significantly increased the contractile response to serotonin (10(-9) to 10(-5) mol/L) only in WKY. The anti-contractile effect of fat was confirmed by a comparison of (+) fat and (-) fat mesenteric arteries, which revealed that 4-AP significantly enhanced contractions only in (+) fat rings from WKY. These results show that alterations in visceral periadventitial fat mass and function in SHR precede hypertension, suggesting a constitutive mechanism independent of age and the hypertensive state.