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1 Department of Physiology, Tulane University Health Sciences Center, New Orleans, LA, USA
2 Department of Medical and Radiological Sciences, The University of Edinburgh, Edinburgh, United Kingdom
* To whom correspondence should be addressed. E-mail: mpatters{at}tulane.edu.
Transient exposure to angiotensin II (ANG II) results in the development of salt-sensitive hypertension in rats. This study was performed to determine if a transient hypertensive episode can induce salt-sensitive hypertension in transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name: TGR(Cyp1a1Ren2)]. Systolic blood pressures were measured in conscious male Cyp1a1-Ren2 rats (n=6) during control conditions and during dietary administration of indole-3-carbinol (I3C, 0.15%, w/w), for 14 days. Systolic pressure increased from 135±5 to 233±7 mmHg by day 14. I3C administration was terminated and blood pressure returned to normal levels (137±5 mmHg) within 10 days. Subsequently, the rats were placed on a high salt diet (8% NaCl) for 10 days. Systolic pressure increased by 34±2 mmHg throughout 10 days of high salt diet. Neither GFR nor RPF were altered in Cyp1a1-Ren2 rats with saltsensitive hypertension. In a separate group of male Cyp1a1-Ren2 rats (n=6) transiently induced with 0.15% I3C for 14 days, administration of the superoxide dismutase mimetic tempol (4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, 2mM) attenuated the increase in systolic pressure induced by high salt. Systolic pressure increased by only 11±1 mmHg throughout 8 days of high salt diet and tempol administration. Thus, transient induction of ANG II-dependent hypertension via activation of the Cyp1a1-Ren2 transgene induces salt-sensitive hypertension in these transgenic rats. The attenuation by tempol of the high salt-induced blood pressure elevation indicates that ANG IIinduced production of superoxide anion contributes to the development of salt-sensitive hypertension after transient induction of ANG II-dependent hypertension.
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