Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat.
BACKGROUND
Tempol is a permeant nitroxide superoxide dismutase (SOD) mimetic that lowers mean arterial pressure (MAP) in spontaneously hypertensive rats (SHRs). We investigated the hypothesis that the antihypertensive response entails a negative salt balance, blunting of plasma renin activity (PRA), endothelin-1 (ET-1), or catecholamines or correction of oxidative stress as indexed by 8-isoprostane prostaglandin F(2alpha) (PGF(2alpha)) (8-Iso).


METHODS
Groups (N= 6 to 8) of SHRs were infused for 2 weeks with vehicle or tempol (200 nmol/kg/min) or given tempol (2 mmol/L) in drinking water.


RESULTS
Tempol infusion reduced the MAP of anesthetized SHRs (150 +/- 5 vs. 126 +/- 6 mm Hg) (P < 0.005). Oral tempol did not change the heart rate but reduced the MAP of conscious SHRs (-23 +/- 6 mm Hg) (P < 0.01) but not Wistar-Kyoto (WKY) rats. Tempol infusion increased the PRA (2.2 +/- 0.2 vs. 5.0 +/- 0.9 ng/mL/hour) (P < 0.005), did not change excretion of nitric oxide (NO) [NO(2)+ NO(3) (NOx)], ET-1, or catecholamines but reduced excretion of 8-Iso (13.2 +/- 1.4 vs. 9.6 +/- 0.9 ng/24 hours; P < 0.01). Cumulative Na(+) balance and gain in body weight were unaltered by tempol infusion. Tempol prevented a rise in MAP with high salt intake.


CONCLUSIONS
Tempol corrects hypertension without a compensatory sympathoadrenal activation or salt retention. The response is independent of nitric oxide, endothelin, or catecholamines and occurs despite increased PRA. It is accompanied by a reduction in oxidative stress and is maintained during increased salt intake.
Welch
William J
WJ
School of Pharmacy, University of Missouri, Kansas City, Missouri, USA.
Mendonca
Margarida
M
Blau
Jonathan
J
Karber
Alex
A
Dennehy
Kathryn
K
Patel
Kinjal
K
Lao
Yuen-Sum
YS
José
Pedro A
PA
Wilcox
Christopher S
CS
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D019332:Endothelin-1 / Q000097:blood; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D012965:Sodium Chloride / Q000378:metabolism; D013113:Spin Labels
D000975:Antioxidants; D002395:Catecholamines; D003497:Cyclic N-Oxides; D019332:Endothelin-1; D013113:Spin Labels; C075750:8-epi-prostaglandin F2alpha; D012965:Sodium Chloride; D015237:Dinoprost; D012083:Renin; C001803:tempol