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Changes in the vascular β ‐adrenoceptor‐activated signalling pathway in 2Kidney‐1Clip hypertensive rats
Author(s) -
Callera Glaucia E,
Yeh Ester,
Tostes Rita C A,
Caperuto Luciana C,
Carvalho Carla R O,
Bendhack Lusiane M
Publication year - 2004
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705717
Subject(s) - isoprenaline , endocrinology , medicine , vasodilation , glibenclamide , forskolin , chemistry , adenosine , protein kinase a , kinase , receptor , stimulation , biochemistry , diabetes mellitus
β ‐Adrenoceptor ( β ‐AR)‐mediated vasodilation, which plays an important physiological role in the regulation of vascular tone, is decreased in two‐kidney, one clip (2K‐1C) renal hypertension. In this study, downstream pathways related to vascular β ‐AR activation were evaluated in 2K‐1C rats. Relaxation responses to isoprenaline, forskolin and 8‐Br‐cAMP were diminished in aortas without endothelium from 2K‐1C when compared to those in normotensive two kidney (2K). Basal adenosine‐3′,5′‐monophosphate (cAMP), as well as isoprenaline‐induced increase in cAMP levels, was not different between 2K and 2K‐1C aortas. Contractile responses to caffeine, after depletion and reloading of intracellular Ca 2+ stores, were greater in 2K‐1C than in 2K. The presence of isoprenaline during the Ca 2+ ‐reloading period abolished the differences between groups by increasing caffeine contraction in 2K without changing this response in 2K‐1C aortas. Inhibition of the sarcolemmal Ca 2+ ATPase with thapsigargin markedly attenuated isoprenaline vasodilation in both 2K and 2K‐1C and abolished the differences between groups. Blockade of ATP‐sensitive K + channels (K ATP ) channels with glibenclamide significantly decreased isoprenaline vasodilation in 2K‐1C without affecting this response in 2K. Both vascular gene and protein expression of protein kinase A (PKA), as well as phosphoserine‐containing proteins, were increased in 2K‐1C vs 2K rats. In conclusion, decreased isoprenaline vasodilation in 2K‐1C hypertensive rats is related to impaired modulation of the sarcolemmal Ca 2+ ATPase activity. Moreover, K ATP channels may play a compensatory role on isoprenaline‐induced relaxation in renal hypertension. Both Ca 2+ ATPase and K ATP channel functional alterations, associated with decreased β ‐AR vasodilation, are paralleled by an upregulation of protein kinase A (PKA) and phosphoserine proteins expression.British Journal of Pharmacology (2004) 141 , 1151–1158. doi: 10.1038/sj.bjp.0705717