In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 290, No. 1 ( 2006-01), p. R145-R153
Abstract:
Although insulin resistance (IR) is a major risk factor for coronary artery disease, little is known about the regulation of coronary vascular tone in IR by endothelin-1 (ET-1). We examined ET-1 and PGF 2α -induced vasoconstriction in isolated small coronary arteries (SCAs; ∼250 μM) of Zucker obese (ZO) rats and control Zucker lean (ZL) rats. ET-1 response was assessed in the absence and presence of endothelin type A (ET A ; BQ-123), type B (ET B ; BQ-788), or both receptor inhibitors. ZO arteries displayed reduced contraction to ET-1 compared with ZL arteries. In contrast, PGF 2α elicited similar vasoconstriction in both groups. ET A inhibition diminished the ET-1 response in both groups. ET B inhibition alone or in combination with ET A blockade, however, restored the ET-1 response in ZO arteries to the level of ZL arteries. Similarly, inhibition of endothelial nitric oxide (NO) synthase with N ω -nitro-l-arginine methyl ester (l-NAME) enhanced the contraction to ET-1 and abolished the difference between ZO and ZL arteries. In vascular smooth muscle cells from ZO, ET-1-induced elevation of myoplasmic intracellular free calcium concentration ([Ca 2+ ] i ) (measured by fluo-4 AM fluorescence), and maximal contractions were diminished compared with ZL, both in the presence and absence of l-NAME. However, increases in [Ca 2+ ] i elicited similar contractions of the vascular smooth muscle cells in both groups. Analysis of protein and total RNA from SCA of ZO and ZL revealed equal expression of ET-1 and the ET A and ET B receptors. Thus coronary arteries from ZO rats exhibit reduced ET-1-induced vasoconstriction resulting from increased ET B -mediated generation of NO and diminished elevation of myoplasmic [Ca 2+ ] i .
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.00405.2005
Language:
English
Publisher:
American Physiological Society
Publication Date:
2006
detail.hit.zdb_id:
1477297-8
SSG:
12
