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The Local Vascular Activity of Norepinephrine (NE) in Renal Perivascular Adipose Tissue (PVAT)

Perivascular adipose tissue (PVAT) is implicated in the pathophysiology of cardiovascular disease, especially in obese individuals in which the quantity of PVAT is markedly increased. We have shown previously that PVAT around the aorta and mesenteric arteries contains releasable norepinephrine (NE) that can constrict the underlying arteries. Although obesity in known to be especially associated with increased noradrenergic activity to the kidneys, and PVAT is found adjacent to the main renal arteries and their primary branches, it is not known if NE derived from PVAT affects the tone of the renal vessels. Therefore, in this study we tested the hypothesis that PVAT around the main kidney artery contains sufficient releasable NE to cause arterial contraction. Tissue NE concentration was measured by High Performance Liquid Chromatography (HPLC). Isometric vascular contractility studies were performed using endothelium intact rings (2 mm) from the main renal artery of normal male Sprague‐Dawley rats. Some rings were studied with PVAT still attached (+PVAT), while others had PVAT removed (−PVAT). Tyramine (Tyr), an indirectly acting sympathomimetic, was used to test for the presence of a functional NE pool in PVAT. Tyr concentration‐response curves (10−8–10−3M) were constructed in the presence of nisoxetine [a NE transporter inhibitor (Nxt: 1 μM)] or vehicle (water). Prazosin (Pz: 1μM), an α1‐adrenoreceptor antagonist, was added after the maximum contraction‐induced by Tyr was obtained. NE concentration (ng/g tissue) was high in main renal arteries and their branches of −PVAT strips (913.9±68.2; n=4) and in isolated PVAT taken from these vessels (523.7±68; n=5). Presence of PVAT did not alter the efficacy of Tyr‐induced contraction, indicated by the concentration to produce the maximum effect (+PVAT: 12.3±3.3mN, − PVAT: 14.5±1.3mN; n= 4–5) or the potency, indicated by the negative logarithm (−log) of half maximal effective concentration (EC50) (+PVAT: −4.1±0.1, − PVAT: −4.6±0.1; n=4–5). Similarly, both pharmacological parameters of Tyr‐induced contraction were not altered by the Nxt: after incubation with Nxt, the efficacy of Tyr‐induced contraction +PVAT was 14.4±3.1mN (n=8) and −PVAT= 10.9±2.9mN (n=5) and its potency +PVAT was −3.7±0.1 (n=8), and −PVAT= −3.74±0.2 (n=5). Pz reduced the maximum effect of Tyr by 90±5% in all of the rings. We conclude that Tyr‐induced contraction of the renal arteries is due to α1‐adrenoreceptor activation by release of NE in a manner independent of PVAT and the NE transporter. Furthermore, and contrary to our hypothesis, it is likely that the effects of Tyr are due exclusively to the release of NE from sympathetic nerves ‐‐ densely present in renal vessels – and not to release of NE from adjacent PVAT.