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Increased NO-Dependent Dilation of Rat Arterioles in Diet-Induced Obesity
Abstract   Peer reviewed

Increased NO-Dependent Dilation of Rat Arterioles in Diet-Induced Obesity

L Howitt, Shaun L Sandow, T Hilton Grayson, M J Morris and T V Murphy
Hypertension, Vol.55(6), p.1499
High Blood Pressure Research Council of Australia Annual Scientific Meeting, 31st (Sydney, Australia, 01-Dec-2009–03-Dec-2009)
2010
DOI: https://doi.org/10.1161/HYP.0b013e3181df4279
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https://doi.org/10.1161/HYP.0b013e3181df4279View
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Abstract

Clinical Sciences Cardiovascular Medicine and Haematology diet-induced obesity rat arterioles
Obesity is an established risk factor for hypertension and associated cardiovascular disease and impairs blood vessel function. The large-conductance Ca2-activated potassium channel (BKCa) in vascular smooth muscle plays a central role in the regulation of vascular tone and we previously reported BKCa function in rat skeletal muscle arterioles is impaired in diet-induced obesity. The aim of this study was to examine the effect of diet-induced obesity on endothelium- and BKCa-dependent dilation of rat skeletal muscle arterioles. Male Sprague- Dawley rats (7-8 weeks) were fed a cafeteria-style high fat or control diet for 16 weeks. Following anesthesia with sodium thiopentone (100 mg/kg i.p.), studies were performed in isolated, pressurized (70 mmHg) first-order arterioles from the cremaster muscle. Control rats weighed 570 7 g compared with obese rats 768 13 g (n 35-37 of each, P 0.05). Electron microscopy of cremaster muscle arterioles showed remodeling associated with obesity, with both media thickness and media to lumen ratio significantly increased in diet-induced obese rats (n 10 of each). Despite this, diet-induced obesity had no effect on acetylcholine (ACh; 0.001-3 M)-induced dilation of arterioles. The NOS and guanylate cyclase (GC) inhibitors L-NAME (100 M) and ODQ (10 M) did not alter myogenic tone in arterioles from control rats, however in arterioles from obese rats diameter was significantly reduced (obese baseline 45.5 1.2% v L-NAME/ODQ 38.1 1.6%, n 21, P 0.05). ACh-induced dilation of arterioles from control rats was completely abolished by a combination of the IKCa, SKCa and BKCablockers TRAM-34 (0.1 M), apamin (0.1 M) and iberiotoxin (IBTX, 0.1 M) respectively, with no apparent role for NO as assessed by the lack of effect of L-NAME/ODQ (n 10-15 of each). In arterioles from obese rats however, IBTX had no effect on responses to ACh while the NO/GC inhibitors partially inhibited ACh-induced dilation (maximum, 3 M ACh, 97.2 1.2% v maximum L-NAME/ODQ 82.6 2.7%, n 12-15 of each, P 0.05). Western blotting showed decreased expression of the BKCa 1-subunit in arterioles from obese rats. Expression of eNOS was not altered by obesity, however there was an accumulation of complexed forms of caveolin-1 and -2 at cremaster arteriole membranes. In summary, diet-induced obesity resulted in an alteration in the relative contribution of NO and BKCa to ACh-mediated endothelium-dependent dilation of rat cremaster muscle arterioles. BKCa-dependent dilation was abolished in obesity while an NO-component was established.

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