Salt-sensitive hypertension develops after transient induction of ANG II-dependent hypertension in Cyp1a1-Ren2 transgenic rats.
Transient exposure to ANG II results in the development of salt-sensitive hypertension in rats. This study was performed to determine whether a transient hypertensive episode can induce salt-sensitive hypertension in transgenic rats with inducible expression of the mouse Ren2 renin gene [strain name TGR(Cyp1a1-Ren2)]. 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%, wt/wt), 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 the high-salt diet. Neither glomerular filtration rate nor renal plasma flow was altered in Cyp1a1-Ren2 rats with salt-sensitive 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, 2 mM) attenuated the increase in systolic pressure induced by high salt. Systolic pressure increased by only 11 +/- 1 mmHg throughout 8 days of a 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 II-induced production of superoxide anion contributes to the development of salt-sensitive hypertension after transient induction of ANG II-dependent hypertension.
Howard
Laura L
LL
Dept. of Physiology, Tulane Univ. Health Sciences Ctr., 1430 Tulane Ave., SL39, New Orleans, LA 70112, USA.
Patterson
Matthew E
ME
Mullins
John J
JJ
Mitchell
Kenneth D
KD
D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D000975:Antioxidants / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004195:Disease Models, Animal; D005919:Glomerular Filtration Rate; D006977:Hypertension, Renal / Q000503:physiopathology*; D007211:Indoles / Q000494:pharmacology; D051379:Mice; D051381:Rats; D012079:Renal Circulation; D012083:Renin / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D000975:Antioxidants; D007211:Indoles; D017673:Sodium Chloride, Dietary; D000804:Angiotensin II; C016517:indole-3-carbinol; D019363:Cytochrome P-450 CYP1A1; D012083:Renin