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Perivascular adipose tissue produces leptin and induces vasorelaxation by opening of 4-aminopyridine (4-AP)-sensitive K+ channels in normotensive rats. We characterized the mesenteric perivascular adipose tissue from 3-month-old Wistar Kyoto (WKY) and aged-matched spontaneously hypertensive rats (SHR) and tested the hypothesis that this tissue contributes to differences in vascular resistance in hypertension. Mesenteric bed (MB) weight and MB total lipid content were lower in SHR than in WKY rats. Freshly isolated MB adipocytes were similar in size between strains. Plasma tryglicerides, glycerol, non-esterified free-fatty acids, and leptin were also lower in SHR than in WKY rats. There was a significant correlation between leptin content and the quantity of mesenteric fat. To study vascular function, the MB was cannulated and perfused at a constant flow of 2 ml/min. 4-AP (2 mM) induced a smaller increase in perfusion pressure in MB of SHR rats, compared to WKY rats. In isolated mesenteric artery rings, 4-AP (2 mM) induced a contractile effect that was significantly reduced in SHR, compared to WKY rats. The anti-contractile effects of perivascular fat were smaller in mesenteric artery rings from SHP rats than from WKY rats. These results suggest that the lower content of perivascular adipose tissue and leptin in SHR might contribute to the increased vascular resistance in this strain. [ABSTRACT FROM AUTHOR]

Leptin causes vasodilatation both by endothelium-dependent and -independent mechanisms. Leptin is synthesized by perivascular adipose tissue (PVAT). The hypothesis of this study is that a decrease of leptin production in PVAT of spontaneously hypertensive rats (SHR) might contribute to a diminished paracrine anticontractile effect of the hormone. We have determined in aorta from Wistar-Kyoto (WKY) and SHR (i) leptin mRNA and protein levels in PVAT, (ii) the effect of leptin and PVAT on contractile responses, and (iii) leptin-induced relaxation and nitric oxide (NO) production. Leptin mRNA and protein expression were significantly lower in PVAT from SHR. Concentration-response curves to angiotensin II were significantly blunted in presence of PVAT as well as by exogenous leptin (10(-9) M) only in WKY. This anticontractile effect was endothelium-dependent. Vasodilatation induced by leptin was smaller in SHR than in WKY, and was also endothelium-dependent. Moreover, release of endothelial NO in response to acute leptin was higher in WKY compared to SHR, but completely abolished in the absence of endothelium. In conclusion, the reduced anticontractile effect of PVAT in SHR might be attributed to a reduced PVAT-derived leptin and to an abrogated effect of leptin on endothelial NO release probably due to an impaired activation of endothelial NO synthase.

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.