The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats.
OBJECTIVE
The following studies were designed to test the hypothesis that Ang (1-7) contributes to the chronic hypotensive effects of the angiotensin II AT(1)-receptor antagonist, losartan, in normal rats.


BACKGROUND
We have previously shown a chronic, hypotensive response to the AT(1)-receptor antagonist, losartan, in normotensive rats. The mechanism of this response is not completely understood. Previous studies by others have demonstrated a role for Ang (1-7) in the beneficial antihypertensive effects of angiotensin-converting enzyme (ACE) inhibition. This is thought to be due to vasodilatory effects of increased levels of Ang (1-7) during ACE inhibition. Since it has now been shown that Ang (1-7) levels are also increased during AT(1) antagonism, we designed experiments to test the hypothesis above.


METHODS
Sprague-Dawley rats were instrumented with venous catheters and radiotelemetric pressure transducers and commenced on a normal (0.4%) NaCl diet. Arterial pressure responses were measured in rats treated with losartan (10 mg/kg/day) (LOS rats, n=8) and compared with those treated with losartan and the Ang (1-7) antagonist, A779 (24 g/kg/hour) (A779/LOS rats, n=11) for 10 days.


RESULTS
By day 7 of treatment, mean arterial pressure had dropped by 27+1 mmHg in LOS rats, in contrast with a decrease of only 21+2 mmHg in A779/LOS rats. This attenuated response in rats treated with A779 became more prominent and continued through day 10 of losartan treatment.


CONCLUSIONS
These results support the hypothesis that the chronic hypotensive effects of losartan in normal rats are mediated in part through the actions of Ang (1-7).
Collister
John P
JP
University of Minnesota, Department of Veterinary PathoBiology, St. Paul 55108, USA. colli066@tc.umn.edu
Hendel
Michael D
MD
D000803:Angiotensin I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C092006:7-Ala-angiotensin (1-7); D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D019808:Losartan