Copyright © 2004, European Society of Cardiology
Renovascular effects of sympathetic cotransmitters ATP and NPY are age-dependent in spontaneoulsy hypertensive rats
Department of Internal Medicine I, Marienhospital Herne, Ruhr-University Bochum, Hölkeskampring 40, 44625 Herne, Germany
* Corresponding author. Medizinische Klinik I, Marienhospital Herne, Klinikum der Ruhr-Universität Bochum, Hölkeskampring 40 D-44625 Herne, Germany. Tel.: +49 2323 499 1671; fax: +49 2323 499 302. Email address: christian.rump{at}ruhr-uni-bochum.de
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 
-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 ,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.
KEYWORDS Autonomic nervous system; Peptide hormones; Hypertension; Neurotransmitters; Receptors
Time for primary review 8 days
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