title: Renovascular effects of sympathetic cotransmitters ATP and NPY are age-dependent in spontaneously hypertensive rats.
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 alpha-adrenoceptor antagonist phentolamine (1 microM) but abolished by the P2 receptor blocker suramin (100 microM). 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 microM) 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 microM) was unable to potentiate RNS-induced, phentolamine-resistant pressor responses in adult SH-SP rats. NE and the stable ATP analogue alpha,beta-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.
authors.affiliation: Department of Internal Medicine I, Marienhospital Herne, Ruhr-University Bochum, Hölkeskampring 40, 44625 Herne, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Vonend
authors.forename: Axel
authors.initials: A
authors.lastname: Okonek
authors.forename: Johannes
authors.initials: J
authors.lastname: Stegbauer
authors.forename: Sina
authors.initials: S
authors.lastname: Habbel
authors.forename: Ivo
authors.initials: I
authors.lastname: Quack
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Rump
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors / Q000235:genetics; D011983:Receptors, Purinergic / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: C092926:BIBP 3226; D009478:Neuropeptide Y; D012333:RNA, Messenger; D017476:Receptors, Neuropeptide Y; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D001120:Arginine; D009638:Norepinephrine