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Increased NO‐dependent dilation of rat arterioles in diet‐induced obesity
Author(s) -
Howitt Lauren,
Grayson T Hilton,
Morris Margaret J,
Murphy Timothy V
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb537
Subject(s) - iberiotoxin , endocrinology , medicine , cremaster muscle , enos , apamin , acetylcholine , chemistry , vasodilation , endothelium , potassium channel , obesity , nitric oxide , microcirculation , nitric oxide synthase
Obesity is a risk factor for hypertension. The large‐conductance Ca 2+ ‐activated potassium channel (BK Ca ) plays a central role in the regulation of vascular tone. The aim of this study was to examine the effect of diet‐induced obesity on endothelium‐ and BK Ca ‐dependent dilation of rat cremaster muscle arterioles. Male Sprague‐Dawley rats (213 ± 1g) were fed a high fat or control diet for 16 weeks. Isolated, pressurized (70 mmHg) arterioles were studied. Control rats weighed 570 ± 7 g compared with obese rats 768 ± 13 g (n = 35 – 37, P < 0.05). Obesity had no effect on acetylcholine (ACh; 0.001 – 3 μM)‐induced dilation. ACh‐induced dilation of arterioles from control rats was abolished by a combination of the SK Ca , IK Ca , and BK Ca blockers apamin, TRAM‐34 and iberiotoxin (IBTX, 0.1 μM) respectively, with no apparent role for NO. In arterioles from obese rats however, IBTX had no effect on responses to ACh while the NO/GC inhibitors L‐NAME (100 μM)/ODQ (10 μM) partially inhibited ACh‐induced dilation. Removal of the endothelium constricted arterioles from obese, but not control rats. Expression of eNOS was not altered by obesity, but expression of high molecular‐weight complexes of caveolin‐1 and ‐2 was increased. In summary, diet‐induced obesity abolished the contribution of BK Ca to ACh‐mediated endothelium‐dependent dilation of rat cremaster muscle arterioles, while inducing an NO‐component. Support: NHMRC 455243.