Studies in this grant are designed to determine how specific stimulation of renal vasopressin Vl receptors can influence the distribution of renal blood flow, sodium and water excretion, urine concentration, and the long-term level of arterial pressure. We will study the effects of acute renal artery and medullary interstitial infusions of arginine vasopressin (AVP), a Vl receptor agonist, and a Vl antagonist on the distribution of renal blood flow and the relationship of such changes on sodium and water excretion. These studies will use techniques including implanted optical fibers for laser-Doppler flowmetry to determine changes of cortical and medullary flow and fluorescent videomicroscopy and servonull pressure measuring techniques to study vasa recta hemodynamics. Other studies utilizing optical fibers chronically implanted in the cortex and medulla will determine the effects of endogenous AVP secretion on the distribution of renal blood flow during dehydration and over-hydration in unanesthetized rats. Instrumented awake rats also will be used to study long-term changes of renal medullary and cortical blood flow, arterial pressure and cardiac output associated with development of hypertension using a new model produced by the long-term infusion of a Vl receptor agonist into the renal medullary interstitial space.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL049219-03
Application #
2225332
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1993-01-01
Project End
1995-12-31
Budget Start
1995-01-01
Budget End
1995-12-31
Support Year
3
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Medical College of Wisconsin
Department
Physiology
Type
Schools of Medicine
DUNS #
073134603
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Mori, Takefumi; Polichnowski, Aaron; Glocka, Padden et al. (2008) High perfusion pressure accelerates renal injury in salt-sensitive hypertension. J Am Soc Nephrol 19:1472-82
Mori, Takefumi; O'Connor, Paul M; Abe, Michiaki et al. (2007) Enhanced superoxide production in renal outer medulla of Dahl salt-sensitive rats reduces nitric oxide tubular-vascular cross-talk. Hypertension 49:1336-41
O'Connor, Paul M; Cowley Jr, Allen W (2007) Vasopressin-induced nitric oxide production in rat inner medullary collecting duct is dependent on V2 receptor activation of the phosphoinositide pathway. Am J Physiol Renal Physiol 293:F526-32
Abe, Michiaki; O'Connor, Paul; Kaldunski, Mary et al. (2006) Effect of sodium delivery on superoxide and nitric oxide in the medullary thick ascending limb. Am J Physiol Renal Physiol 291:F350-7
Morrison, Jolean; Knoll, Kristen; Hessner, Martin J et al. (2004) Effect of high glucose on gene expression in mesangial cells: upregulation of the thiol pathway is an adaptational response. Physiol Genomics 17:271-82
Cowley Jr, Allen W; Mori, Takefumi; Mattson, David et al. (2003) Role of renal NO production in the regulation of medullary blood flow. Am J Physiol Regul Integr Comp Physiol 284:R1355-69
Yuan, Baozhi; Liang, Mingyu; Yang, Zhizhang et al. (2003) Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of renal outer medulla to nonhypertensive elevations of ANG II. Am J Physiol Regul Integr Comp Physiol 284:R1219-30
Mori, Takefumi; Dickhout, Jeffrey G; Cowley Jr, Allen W (2002) Vasopressin increases intracellular NO concentration via Ca(2+) signaling in inner medullary collecting duct. Hypertension 39:465-9
Yuan, B; Cowley Jr, A W (2001) Evidence that reduced renal medullary nitric oxide synthase activity of dahl s rats enables small elevations of arginine vasopressin to produce sustained hypertension. Hypertension 37:524-8
Cowley Jr, A W (2000) Control of the renal medullary circulation by vasopressin V1 and V2 receptors in the rat. Exp Physiol 85 Spec No:223S-231S

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