Hypotensive effects of the angiotensin II antagonist telmisartan in conscious chronically-instrumented transgenic rats.
The effects after oral administration of the angiotensin II antagonist telmisartan (CAS 144701-48-4, BIBR 227) on arterial blood pressure and heart rate of conscious chronically-instrumented TGR (mREN2)27 transgenic rats were studied. Each dose of telmisartan (0.5, 1 and 2 mg/kg) was given for one week via the drinking water to transgenic rats and cardiovascular parameters were monitored via telemetry. Losartan and captopril were given for comparison. Telmisartan dose-dependently decrease mean arterial blood pressure by -33 mmHg at 0.5 mg/kg/d, -57 mmHg at 1 mg/kg/d, and -72 mmHg at 2 mg/kg/d. Heart rate was lowered by -33 bpm at the lowest dose and -39 bpm at the highest dose of telmisartan. The reference compounds losartan and captopril given via the drinking water also lowered blood pressure in these transgenic rats. The decreases in mean arterial blood pressure amounted to -13 mmHg at 1 mg/kg/d, -22 mmHg at 2 mg/kg/d and -33 mmHg at 4 mg/kg/d losartan and -54 mmHg at 10 mg/kg/d captopril. In general, heart rates slightly decreased after oral administration of both compounds. These data show that telmisartan was an effective antihypertensive agent in these transgenic rats at oral doses of > or = 0.5 mg/kg/d. The compound was more potent than losartan in reducing mean arterial blood pressure in the TGR (mREN)27 transgenic rats.
van Meel
J C
JC
Department of Biological Research, Dr. Karl Thomae GmbH, Biberach/Riss, Germany.
Redemann
N
N
Haigh
R M
RM
D000284:Administration, Oral; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000008:administration & dosage; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics; D002216:Captopril / Q000008:administration & dosage; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage; D019808:Losartan; D051381:Rats; D000077333:Telmisartan; D013777:Tetrazoles / Q000008:administration & dosage
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001565:Benzoates; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan; D000077333:Telmisartan