(Hypertension. 1995;26:249-255.)
© 1995 American Heart Association, Inc.
Articles |
Nitric Oxide Synthase Inhibition in Spontaneously Hypertensive Rats
Systemic, Renal, and Glomerular Hemodynamics
Presented at the 27th Annual Meeting of the American Society of Nephrology, Orlando, Fla, October 26-29, 1994, and published in abstract form (J Am Soc Nephrol. 1994;3:548).
From the Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, La.
Abstract To investigate the prolonged effects of nitric oxide
inhibition on systemic, renal, and glomerular
hemodynamics, the effects of the nitric oxide synthase
inhibitor
N
-nitro-L-arginine methyl ester
(L-NAME) on cardiac index, renal micropuncture results, urinary
excretion, and histology were obtained in 20-week-old male
spontaneously hypertensive rats (SHR) that were divided into two
groups: untreated and L-NAME–treated (50 mg/L), each followed for 3
weeks. Cardiac index and effective renal plasma flow decreased
(P<.01) in L-NAME–treated SHR, exhibiting a positive
correlation (r=.816; P<.0001). Single-nephron
plasma flow (123±8 versus 80±12 nL/min per gram; P<.01)
and ultrafiltration coefficient (P<.05) were also reduced
in L-NAME–treated SHR versus controls. Most notably, the
L-NAME–treated SHR had increased afferent (4.4±0.3 versus 9.5±1.3 U;
P<.01) and efferent (1.4±0.1 versus 2.7±0.3 U;
P<.01) glomerular arteriolar resistances versus
controls. These functional changes were associated with significantly
altered afferent arteriolar (P<.001) and
glomerular (P<.005)
histological injury scores accompanied by marked
proteinuria (P<.001). Because of the intense afferent
glomerular artery constriction and lesser increase in
efferent glomerular arteriolar resistance associated with
reduced single-nephron plasma flow, glomerular capillary
pressure did not increase in the L-NAME–treated SHR. Thus, L-NAME
produced marked proteinuria and severe hypertensive
nephrosclerosis manifested by afferent arteriolar
fibrinoid necrosis, segmental glomerular hyalinosis and
sclerosis, and myocardial fibrosis without any further increase in left
ventricular mass, thereby providing a new model for severe
hypertensive nephrosclerosis in young SHR without the
necessity for surgical reduction of renal mass.
Key Words: nitric oxide • hypertension, L-NAME • cardiac output • renal micropuncture • nephrosclerosis • rats, inbred SHR
This article has been cited by other articles:
 |
|
 |
|
  S. Sethi, S. Iida, C. D. Sigmund, and D. D. Heistad Renal Thrombotic Microangiopathy in a Genetic Model of Hypertension in Mice Experimental Biology and Medicine, February 1, 2006; 231(2): 196 - 203. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. F. Benter, M. H. M. Yousif, J. T. Anim, C. Cojocel, and D. I. Diz Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H684 - H691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Zhou and E. D. Frohlich Ageing, hypertension and the kidney: new data on an old problem Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1442 - 1445. [Full Text] [PDF]
|
|
|
|
|
|
X. Zhou and E. D. Frohlich Ageing, hypertension and the kidney: new data on an old problem Nephrol. Dial. Transplant., August 1, 2003; 18(88): 1442 - 1445. [Full Text]
|
|
|
|
 |
|
 N. Toda and T. Okamura The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels Pharmacol. Rev., June 1, 2003; 55(2): 271 - 324. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mori, T. Nishikimi, N. Kobayashi, H. Ono, K. Kangawa, and H. Matsuoka Long-Term Adrenomedullin Infusion Improves Survival in Malignant Hypertensive Rats Hypertension, July 1, 2002; 40(1): 107 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ono, Y. Ono, A. Takanohashi, H. Matsuoka, and E. D. Frohlich Apoptosis and Glomerular Injury After Prolonged Nitric Oxide Synthase Inhibition in Spontaneously Hypertensive Rats Hypertension, December 1, 2001; 38(6): 1300 - 1306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Frohlich Local Hemodynamic Changes in Hypertension: Insights for Therapeutic Preservation of Target Organs Hypertension, December 1, 2001; 38(6): 1388 - 1394. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, H. Ono, X. Zhou, and E. D. Frohlich Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N{{omega}}-Nitro-L>-Arginine Methyl Ester/Spontaneously Hypertensive Rats Hypertension, May 1, 2001; 37(5): 1262 - 1267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D Frohlich Review: Promise of prevention and reversal of target organ involvement in hypertension Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S4 - S9. [PDF]
|
|
|
|
|
|
D. Susic, J. Varagic, and E. D. Frohlich Abnormal Renal Vascular Responses to Dipyridamole-Induced Vasodilation in Spontaneously Hypertensive Rats Hypertension, March 1, 2001; 37(3): 894 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Arai, K. Morimoto, M. Oka, T. Hikita, K. Arai, K. Umezawa, M. Nagase, and T. Yamamoto Aminoguanidine induces haematuria of non-glomerular origin in spontaneously hypertensive rats Nephrol. Dial. Transplant., June 1, 2000; 15(6): 811 - 817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ono, H. Ono, H. Matsuoka, T. Fujimori, and E. D. Frohlich Apoptosis, Coronary Arterial Remodeling, and Myocardial Infarction After Nitric Oxide Inhibition in SHR Hypertension, October 1, 1999; 34(4): 609 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nakamura, H. Ono, and E. D. Frohlich Differential Effects of T- and L-Type Calcium Antagonists on Glomerular Dynamics in Spontaneously Hypertensive Rats Hypertension, August 1, 1999; 34(2): 273 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ichihara, J. D. Imig, and L. G. Navar Neuronal Nitric Oxide Synthase-Dependent Afferent Arteriolar Function in Angiotensin II-Induced Hypertension Hypertension, January 1, 1999; 33(1): 462 - 466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. M. Pollock and A. Rekito Hypertensive response to chronic NO synthase inhibition is different in Sprague-Dawley rats from two suppliers Am J Physiol Regulatory Integrative Comp Physiol, November 1, 1998; 275(5): R1719 - R1723. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Radaelli, L. Mircoli, I. Mori, G. Mancia, and A. U. Ferrari Nitric Oxide–Dependent Vasodilation in Young Spontaneously Hypertensive Rats Hypertension, October 1, 1998; 32(4): 735 - 739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Francischetti, H. Ono, and E. D. Frohlich Renoprotective Effects of Felodipine and/or Enalapril in Spontaneously Hypertensive Rats With and Without L-NAME Hypertension, March 1, 1998; 31(3): 795 - 801. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hayakawa and L. Raij Nitric Oxide Synthase Activity and Renal Injury in Genetic Hypertension Hypertension, January 1, 1998; 31(1): 266 - 270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Frohlich Influence of Nitric Oxide and Angiotensin II on Renal Involvement in Hypertension Hypertension, January 1, 1997; 29(1): 188 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Dohi, M. Kojima, and K. Sato Benidipine Improves Endothelial Function in Renal Resistance Arteries of Hypertensive Rats Hypertension, July 1, 1996; 28(1): 58 - 63. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ono, Y. Ono, and E. D. Frohlich ACE Inhibition Prevents and Reverses L-NAMEExacerbated Nephrosclerosis in Spontaneously Hypertensive Rats Hypertension, February 1, 1996; 27(2): 176 - 183. [Abstract] [Full Text]
|
|