Differential effect of tetradecythioacetic acid on the renin-angiotensin system and blood pressure in SHR and 2-kidney, 1-clip hypertension.
The tetradecythioacetic acid (TTA) is a modified fatty acid known to exhibit pleiotropic effects. First, we compared the effect of TTA on the blood pressure in spontaneously hypertensive rats (SHR) with two-kidney, one-clip (2K1C)-hypertensive rats. Second, we examined mechanisms involved in the blood pressure reduction. TTA had minor effect on systolic blood pressure (SBP) in young SHR up to 8 wk of age. In 2K1C we confirmed the blood pressure-lowering effect of TTA (SBP: 173 +/- 4 before vs. 138 +/- 3 mmHg after TTA, P < 0.001). No effect on SBP was seen in Wistar-Kyoto rat (WKY) controls. Plasma renin activity (PRA) was low in SHR and WKY controls and TTA did not change it. PRA decreased from 22.9 +/- 1.3 to 16.2 +/- 2.2 ng.ml(-1).h(-1) (P = 0.02) in 2K1C. Plasma ANG II concentration declined from 101 +/- 3 to 81 +/- 5 fmol/l after TTA treatment (P = 0.005). In the clipped kidney, tissue ANG I concentration decreased from 933 +/- 68 to 518 +/- 60 fmol/g tissue (P = 0.001), and ANG II decreased from 527 +/- 38 to 149 +/- 21 fmol/g tissue (P < 0.001) after TTA treatment. In the nonclipped kidney, TTA did not change ANG I and moderately reduced ANG II levels. The renal blood flow response to injection of ANG II into the nonclipped kidney was blunted compared with controls and normalized with TTA treatment (10 +/- 2 before vs. 20 +/- 2%, P < 0.001). The results indicate that TTA downregulates the renin-angiotensin system in high renin animals but has no effect in low renin models.
Bivol
Liliana Monica
LM
Renal Research Group, Institute of Medicine, University of Bergen, Bergen, Norway. monica.bivol@med.uib.no
Berge
Rolf Kristian
RK
Iversen
Bjarne Magnus
BM
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051381:Rats; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000494:pharmacology*; D013997:Time Factors
D000959:Antihypertensive Agents; D013438:Sulfhydryl Compounds; C523597:tetradecythioacetic acid; D000804:Angiotensin II; D000803:Angiotensin I