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Hypertensive nephrosclerosis in the Dahl/Rapp rat. Initial sites of injury and effect of dietary L-arginine supplementation.

AbstractBACKGROUND:
The Dahl/Rapp strains of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rat were developed to examine pathogenetic mechanisms that produce hypertension in response to an increase in dietary salt. We have shown that providing SS/Jr rats with L-arginine, the metabolic precursor of nitric oxide, acutely prevented salt-sensitive hypertension, suggesting that SS/Jr rats developed hypertension because of inadequate nitric oxide production while on a high-salt diet.
EXPERIMENTAL DESIGN:
Male 23-day SS/Jr and SR/Jr rats were placed on chow that contained 8% sodium chloride. One group of SS/Jr rats also received L-arginine, 1.25 g/liter, in their drinking water. These three groups were examined at weekly intervals for 4 weeks.
RESULTS:
SS/Jr rats rapidly developed hypertension when placed on the high-salt chow. After 2 weeks on this diet, inulin clearance dramatically decreased, and albumin excretion rate increased. By the fourth week of study, SS/Jr rats on the high-salt diet had died or were dying. Coincident with the progressive decline in inulin clearance, renal morphologic analysis confirmed development of myointimal thickening, fibrinoid necrosis, and glomerulosclerosis. In contrast, over the 4 weeks of study, SS/Jr rats supplemented with oral L-arginine did not develop hypertension and any of the associated renal complications seen in age-matched SS/Jr rats on the high-salt diet. L-Arginine also corrected hypertension in SS/Jr rats exposed to the high-salt chow for 2 weeks before the inception of L-arginine. L-Arginine administration after 3 weeks on this chow, however, failed to reverse hypertension and the depressed inulin clearance and morphologic renal damage.
CONCLUSIONS:
Along with previous work (Chen PY, Sanders PW, J Clin Invest 88:1559-67), these studies were consistent with the hypothesis that hypertension and hypertensive nephrosclerosis developed in SS/Jr rats because, while on a high-salt diet, substrate (L-arginine) became a rate-limiting factor in the synthesis of nitric oxide.
AuthorsP Y Chen, P L St John, K A Kirk, D R Abrahamson, P W Sanders
JournalLaboratory investigation; a journal of technical methods and pathology (Lab Invest) Vol. 68 Issue 2 Pg. 174-84 (Feb 1993) ISSN: 0023-6837 [Print] United States
PMID8441251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Sodium, Dietary
  • Nitric Oxide
  • Arginine
Topics
  • Animals
  • Arginine (administration & dosage, pharmacology)
  • Blood Pressure (drug effects)
  • Diet
  • Hypertension (etiology, pathology, prevention & control)
  • Kidney (pathology, ultrastructure)
  • Male
  • Nephrosclerosis (etiology, pathology, prevention & control)
  • Nitric Oxide (metabolism)
  • Rats
  • Sodium, Dietary (pharmacology)

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