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- Title
Renovascular effects of sympathetic cotransmitters ATP and NPY are age-dependent in spontaneoulsy hypertensive rats
- Authors
Vonend, Oliver; Okonek, Axel; Stegbauer, Johannes; Habbel, Sina; Quack, Ivo; Rump, Lars Christian
- Abstract
Abstract: Objective: Hypertension is characterized by sympathetic overactivity. Neuropeptide Y (NPY) and ATP are cotransmitters of norepinephrine (NE) and regulate renovascular resistance. The present study analyzes sympathetic nonadrenergic neurotransmission in hypertensive (SH-SP) and normotensive (WKY) rats. In addition, adult and young hypertensive rats were compared to investigate the role of aging on sympathetic nonadrenergic cotransmission in hypertensive disease. Methods: Pressor responses to renal nerve stimulations (RNS) and drugs were measured on isolated perfused kidneys of young (8–10 weeks) and adult (18–24 weeks) WKY, and SH-SP rats. Results: RNS evoked contractions at 1 Hz were resistant to blockade by the α-adrenoceptor antagonist phentolamine (1 μM) but abolished by the P2 receptor blocker suramin (100 μM). Compared to adult WKY, RNS-induced pressor responses were unchanged in adult SH-SP and young WKY, but significantly greater in young SH-SP rats. The NPY-Y1 receptor antagonist BIBP3226 (1 μM) reduced phentolamine-resistant pressor responses in adult and young WKY, young SH-SP, but not in adult SH-SP rats. In contrast to WKY and young SH-SP rats, exogenously perfused NPY (0.1 μM) was unable to potentiate RNS-induced, phentolamine-resistant pressor responses in adult SH-SP rats. NE and the stable ATP analogue α,β-mATP increased the perfusion pressor response more potently in adult SH-SP than in WKY rats. Conclusions: Neuronally released NPY plays a major role in potentiating RNS-induced nonadrenergic pressor responses in kidneys of WKY and young SH-SP rats. In adult SH-SP rats NPY fails to enhance these responses. In this hypertensive model ageing seems to be associated with a loss of a modulatory role of renal NPY Y1 receptors. Since pressor responses to NE and ATP are higher in SH-SP animals, functional NPY-Y1 receptor downregulation might be an adaptive mechanism.
- Subjects
HYPERTENSION; NEUROPEPTIDES; LABORATORY rats; DEVELOPMENTAL biology
- Publication
Cardiovascular Research, 2005, Vol 66, Issue 2, p345
- ISSN
0008-6363
- Publication type
Article
- DOI
10.1016/j.cardiores.2004.12.005