Document Detail

Role of neuropeptide Y in the development of two-kidney, one-clip renovascular hypertension in the rat.
MedLine Citation:
PMID:  11054234     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Along with the renin-angiotensin system, sympathetic stimulation may contribute to renovascular hypertension. The vasoactive peptide neuropeptide Y (NPY) is co-released with and potentiates the pressor effects of norepinephrine through the Y-1 receptor. NPY, by exaggerating sympathetic activity, may contribute to renovascular hypertension, possibly by augmenting adrenergic-mediated renin release. This was studied by determining the effect of continuous Y-1 blockade on the development of two-kidney, one-clip renovascular hypertension and the effect of NPY on in vitro renin release.
METHODS: Mean arterial pressure and renal blood flow responses to NPY (10 microg/kg, administered intravenously) were measured in five anesthetized Sprague-Dawley rats before and after BIBO3304TF administration to test the Y-1 antagonist BIBO3304TF. In hypertension studies, 28 rats underwent left renal artery clipping. Of these, 13 were implanted with a mini-osmotic pump for continuous BIBO3304TF infusion (0.3 microg/h, administered intravenously); the other 15 underwent sham implantation. Systolic blood pressure was then monitored for 4 weeks. Finally, in vitro renin release was measured from renal cortical slices (n = 6-12) incubated with NPY (10(-8) to 10(-6) mol/L) or NPY plus the adrenergic agonist isoproterenol (10(-4) mol/L).
RESULTS: BIBO3304TF attenuated the NPY-induced increase in mean arterial pressure by 54% (P <.02) and the NPY-induced decrease in renal blood flow by 38% (P <.05). In 4-week hypertension studies, systolic blood pressure in clipped controls increased from 130 +/- 3 mm Hg to 167 +/- 6 mm Hg (P <.01), whereas BIBO3304TF-treated rats had no significant increase (125 +/- 3 mm Hg to 141 +/- 8 mm Hg). Final systolic blood pressure was 26 mm Hg lower in BIBO3304TF-treated rats than in controls (P <.01). In renal cortical slices, no NPY effect was observed in basal or isoproterenol-stimulated renin release.
CONCLUSIONS: The Y-1 receptor antagonist BIBO3304TF attenuated acute pressor responses to NPY and blunted the development of two-kidney, one-clip renovascular hypertension in rats. NPY may contribute to the hypertensive response in this renovascular hypertension model. Our in vitro data do not suggest that this is due to NPY enhancement of renin release.
L H Shin; P S Dovgan; T J Nypaver; O A Carretero; W H Beierwaltes
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of vascular surgery     Volume:  32     ISSN:  0741-5214     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2000 Nov 
Date Detail:
Created Date:  2000-12-14     Completed Date:  2000-12-14     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1015-21     Citation Subset:  IM    
Divisions of Vascular Surgery and Hypertension and Vascular Research, Henry Ford Hospital, Detroit, MI 48202, USA.
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MeSH Terms
Arginine / analogs & derivatives*
Blood Pressure Determination
Disease Models, Animal
Hemodynamics / physiology
Hypertension, Renal / chemically induced*
Injections, Intravenous
Kidney / physiopathology
Neuropeptide Y / antagonists & inhibitors*
Rats, Sprague-Dawley
Reference Values
Renin / biosynthesis*
Grant Support
Reg. No./Substance:
0/BIBO 3304; 0/Neuropeptide Y; 74-79-3/Arginine; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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