Logo image
Back
Diet-induced obesity does not alter BKCa-mediated responses in rat mid-cerebral arterioles
Abstract   Peer reviewed

Diet-induced obesity does not alter BKCa-mediated responses in rat mid-cerebral arterioles

L Howitt, T Hilton Grayson, Shaun L Sandow, M J Morris and T V Murphy
Journal of Vascular Research, Vol.46(Supplement 2), p.29
Australian and New Zealand Microcirculation Society Meeting, 14th (Queenstown, New Zealand, 25-Aug-2009–27-Aug-2009)
2009
DOI: https://doi.org/10.1159/000230992
url
https://doi.org/10.1159/000230992View
Published Version

Abstract

Medical and Health Sciences diet-induced obesity physiological vasodilation rat mid-cerebral arterioles
Obesity is associated with increased risk of vascular disease, in particular hypertension and cerebrovascular disease. Obesity may inhibit the function of vascular K+-channels, vital for normal, physiological vasodilation. Amongst these, the large-conductance Ca2+-activated potassium channel (BKCa) is critical for the regulation of vascular tone. It is composed of four α pore-forming subunits and four regulatory β1 subunits, which enhance Ca2+- and voltagesensitivity. The aim of this study was to investigate the effect of diet-induced obesity on BKCa expression and function in rat mid-cerebral arterioles (MCA). Male Sprague-Dawley rats (7-8 weeks) were fed a cafeteria-style high fat diet (HFD) or standard chow (control) for 16-20 weeks. At the conclusion of this period, control rats weighed 562±9g compared with HFD (obese) rats 748±14g (n=40 of each, P less than 0.05). Obese rats had significantly increased fat mass (retroperitoneal and testicular) and blood insulin and glucose. Animals were anaesthetized with sodium thiopentone (100mg/kg i.p.). Isolated, pressurized (80mmHg) segments of the MCA were studied, with intra-luminal diameter measured using video microscopy. Protein and mRNA expression of BKCa-α and -β1 subunits in arterioles was measured using Western blotting, immunohistochemistry and RT-PCR. Myogenic tone of arterioles, expressed as a percentage of passive diameter, was not significantly different between control 60.8±2.8% and obese rats 56.8±2.6% (n=13-14 of each). The BKCa antagonist iberiotoxin (IBTX, 0.1μM) constricted MCA from control (59.3±5.4% of passive diameter to 41.1±3.4%, n=6) and obese rats (59.1±3.4% to 40.2±1.8%, n=6) to a similar extent. Dilation induced by the the BKCa-α subunit-selective agonist NS1619 (0.1μM-100μM, n=6-7 of each) was not altered in MCA from obese rats. Dilation to both bradykinin (BK) and sodium nitroprusside (SNP) (0.001μM- 30μM, n=12-13 of each) was not altered in both groups. IBTX (0.1μM) greatly attenuated dilation to NS1619, BK and SNP in arterioles from both control and obese rats (n=5-6 of each). Neither mRNA nor protein expression of BKCa-α subunits were significantly different between MCA from control and obese rats. Expression of BKCa-β1 subunit protein was significantly increased in obese rats (0.37±0.07) compared to control (0.14±0.04), whereas - β1-subunit mRNA expression was not altered. Immunohistochemistry showed BKCa-α and -β1 expression exclusively in smooth muscle cells of MCA. These observations suggest that neither BKCa expression nor BKCa dependent-responses of rat MCA are altered in diet-induced obesity. This is in contrast to our previous findings in arterioles from the rat cremaster muscle, in which both BKCa-β1 expression and BKCa function were inhibited (Howitt et al., 2008).

Details

Metrics

409 Record Views
Logo image