Antihypertensive response to prolonged tempol in the spontaneously hypertensive rat

Abstract

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.

Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats

“…This may be explained on the basis of the inhibition of angiotensin converting enzyme by exogenous H 2 S 47 and the superoxide scavenging activity of exogenously administered tempol. 13,48 It was observed that although both H 2 S and tempol functions in an independent way, the interaction of the two groups results in a greater response. However, the reductions in blood pressure and increased renal excretion observed in the present study after the combination therapy with exogenous H 2 S and tempol are neither additive nor potentiating in a true sense as was hypothesized.…”

“…17,27 In terms of the chronic tempol administration, its antioxidant action 12 is also partly responsible for the reduction in blood pressure which would be in accord with previous reports. 13,18 Moreover, the co-treatment with NaHS and tempol resulted in a significantly greater decrease in systolic blood pressure and mean arterial blood pressure compared with the SHR + NaHS and SHR + tempol groups. Taken together, this suggests that the reductions in blood pressure in the SHR following the combination of NaHS and tempol may be influenced by both the antioxidant activity of tempol 13 and the up-regulation of the CSE enzyme by exogenous NaHS resulting in increased production of endogenous H 2 S. 18 Supporting this argument, there was a marked increase in plasma H 2 S levels and urinary H 2 S excretion.…”

“…13,18 Moreover, the co-treatment with NaHS and tempol resulted in a significantly greater decrease in systolic blood pressure and mean arterial blood pressure compared with the SHR + NaHS and SHR + tempol groups. Taken together, this suggests that the reductions in blood pressure in the SHR following the combination of NaHS and tempol may be influenced by both the antioxidant activity of tempol 13 and the up-regulation of the CSE enzyme by exogenous NaHS resulting in increased production of endogenous H 2 S. 18 Supporting this argument, there was a marked increase in plasma H 2 S levels and urinary H 2 S excretion. On the basis of the above findings, it would appear that a degree of synergism exists between the actions of H 2 S and tempol.…”

“…21 Moreover, a 4-week treatment with tempol significantly increased creatinine clearance in the SHR + tempol treated group suggestive of decreased pre-glomerular arteriolar resistance and is in accord with an earlier study. 13 Furthermore, the combination therapy with exogenous NaHS and tempol improved the creatinine clearance more effectively compared with NaHS or tempol alone. Renal cortical blood perfusion was lower in SHRs compared with the WKY indicating an enhanced renal vasoconstriction along the resistance vasculature.…”

“…11 The acute antihypertensive response to tempol is related to its in vitro superoxide dismutase (SOD)-mimetic activity. 12 However, the long-term outcome of tempol administration in relation to the kidney may well be a correction of salt sensitivity, 13 renal hypoxia, 4 and renal vasoconstriction. 14 Hydrogen sulfide (H 2 S) has attracted a great deal of interest as it can be generated endogenously by the action of two enzymes cystathionine beta synthase (CBS) and cystathionine gamma lyase (CSE) from L-cysteine.…”