(Hypertension. 1997;29:188.)
© 1997 American Heart Association, Inc.
Arthur C. Corcoran Memorial Lecture |
Influence of Nitric Oxide and Angiotensin II on Renal Involvement in Hypertension
From the Alton Ochsner Medical Foundation, New Orleans, LA.
Correspondence to Edward D. Frohlich, MD, Alton Ochsner Medical Foundation, 1516 Jefferson Hwy, New Orleans, LA 70121
Remarkable advances have been made with prolonged antihypertensive therapy in reversing cardiovascular morbidity and mortality. Deaths from stroke have been reduced by 70% and from coronary heart disease by 35%. In contrast, endstage renal disease resulting from hypertension continues to increase. The explanations for this seeming paradox remain unresolved even though experimental models have demonstrated that certain antihypertensive agents may have beneficial renal and intrarenal hemodynamic effects; but reversal of the intrarenal pathological lesions have not been shown to improve. This discussion summarizes recent studies from our laboratory in aged (73- and 85-week-old) spontaneously hypertensive rats (SHR) with naturally occurring end-stage renal disease and in a model of aged SHR employing nitric oxide inhibition in younger, adult (20-week-old) SHR. Our findings demonstrated that the systemic and whole renal hemodynamics, intrarenal glomerular dynamics, proteinuria, and renal pathological lesions can be prevented or reversed with angiotensin-converting enzyme inhibition therapy but not with hydrochlorothiazide (at similar levels of arterial pressure reduction). The implications and possible mechanisms involved in the development of both naturally occurring and nitric oxide-exacerbated SHR are multifactorial, involving the endothelial nitric oxide system and its interaction with angiotensin II (and possibly bradykinin) among other factors. Moreover, these pathophysiological cellular mechanisms may be shared by the aging process as well as in naturally occurring spontaneous hypertension in the rat and, perhaps, in humans with essential hypertension. Thus, antihypertensive therapy seems to be specific in its ability to prevent and even reverse the pathophysiological derangements of renal involvement in hypertension. Thus, prevention and reversal of end-stage renal disease do not seem to require greater reduction of arterial pressure than with other target-organ involvement. However, they do require specific inhibition of the arteriolar and glomerular lesions produced by the disease.
Key Words: endothelium • glomerular disease • arteriolar disease • L-NAME • nitric oxide • L-arginine • angiotensin-converting enzyme inhibition • nephrosclerosis • hydrochlorothiazide
Abbreviations: ACE = angiotensin-converting enzyme • Ang II = angiotensin II • ESRD = end-stage renal disease • L-NAME = No-nitro-L-arginine methyl ester • NO = nitric oxide • SHR = spontaneously hypertensive rat(s)
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