This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text, please contact the Ruth Lilly Medical Library's Interlibrary Loan Department (rlmlill@iu.edu)

Carmines, Pamela Kay

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This document only includes an excerpt of the corresponding thesis or dissertation. To request a digital scan of the full text., please contact the Ruth Lilly Medical Library.,s Interlibrary Loan Department (rlmlill@iu.edu). Role of angiotensin in the vascular response to chronic renal tubular obstruction by Pamela K. Carmines Submitted to the Faculty of the Graduate School in partial fulfillment of the requirements for the degree Doctor of Philosophy in the Department of Physiology, Indiana University May 1982 Accepted by the Fa cu l t y a f th e Grad u at c Schoo l , De p u rt r,1 en t of Physiology, Indiana University, in partial fulfillraent of the requirements for the desree Doctor of Philosophy. Ma,, J Doctoral Co~mittee: Date A--11- {l, 5~ __ George A. Tanner [Chai raanl Professor of Physiology ~~.~ ___ Ewald E. Selkurt Distinguished Professor of Physiology iJ_. H. G Lenn Boh Len Associate Professor of Physiology Jcrsild, Jr. Professor of Anztomy ~----~__::;.----;rfe~----Moo f!ahm Yum Associate Professor of Pathology i V ABSTRACT Chronic (24 hour) obstruction of single tubules of the rat kidney causes a decrease in glomerular blood flow as a result of afferent arteriolar constriction. Since all of the components of the renin-angiotensin system are present in the juxtaglomerular apparatus of each nephron, we investigated the possi bi Li ty that obst ruction-induced vaso-co n strict ion is mediated by intrarenal angiotensin generation. In pentobarbital anesthetized rats, micro-puncture techniques were uti Li zed to inject Long viscous castor oil blocks into the Lumens of 15-20 proximal tubules. The next day, the animals were anesthetized with Inactin and 9 µm microspheres were injected into the circulation at the Left ventricle. For each rat, glomerular blood flow was calculated from the number of trapped microspheres visualized in microdissected normal and obstructed nephrons. Three sets of rats and their vehicle controls were examined by this procedure. The treatments gi van were (I) captopri l, 10 mg/kg, p.a., [II) saralasin, 10 µg/kg/min, i.v., or (III) high salt intake administered in drinking water plus desoxycorticosterone [DOC) injections at an average dosage of 2.7 mg/kg/day for 2-3 weeks. Glomerular blood flow of normal nephrons in control animals averaged 226 ± 12 nl/min (S.E.M., n=17 rats), whi Le blood flow to blocked nephrons was 130 ± 9 nl/min, a 41% decrease in glomerular perfusion (p<0.001). In 5 rats V treated with captopri L, a converting enzyme inhibitor, blood flow to normal nephrons and obstructed nephrons averaged 296 ±. 40 and 252 ±. 31 nl/min, respectively, representing a significant improvement in flow to blocked tubules C p <0 .00 51. In six rats treated with saralasin, an angiotensin antagonist, blood flow to unobstructed nephrons was 210 ±. 11 nl/min, while flow to blocked nephrons averaged 152 ±. 4 nl/min, a significant reduction of the vasoconstriction response to obstruction when compared to control rats [p<0.05). In 6 renin depleted rats [high salt intake and DOC), blood flow to normal and tubule-obstructed nephrons was 229 + 20 and 181 + 21 nl/min, respectively, a si gni fi cant decrease in the difference in flow between normal and blocked nephrons [p<0.0005). Therefore, both renin suppression and pharmacologic intervention of angiotensin action with captopril or saralasin improved glomerular perfusion of obstructed nephrons. This strongly supports the dependence of obstuction-induced changes in arteriolar resistance upon angiotensin activity. These observations support the theory that angiotensin functions as a Locally acting hormonal factor controlling glomerular hemodynamics. ABSTRACT ACKNOWLEDGEMENTS LIST OF FIGURES LIST OF TABLES LIST OF ABBREVIATIONS INTRODUCTION TABLE OF CONTENTS RENIN-ANGIOTENSIN SYSTEM Biochemistry and pharmacology Effects of angiotensin and control of Feedback control of nephron function Renin-angiotensin as a local hormonal URINARY TRACT OBSTRUCTION Acute obstruction Chronic obstruction STATEMENT OF PURPOSES METHODS Production of Tubular Obstruction Microsphere Methodology Experimental Protocols Analyses RESULTS DISCUSSION APPENDICES Appendix A Appendix B Appendix C Appendix D REFERENCES CURRICULUM VITAE renin release system Vi i .Q...s.il i V vi Vi i i i X X 1 1 1 8 1 5 20 23 23 26 32 33 33 34 37 40 42 62 86 86 90 98 117 1 21 135 

Role of angiotensin in the vascular response to chronic renal tubular obstruction

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Role of angiotensin in the vascular response to chronic renal tubular obstruction

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