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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.