Effect of chronic treatment with losartan potassium (DuP 753) on the elevation of blood pressure during chronic exposure of rats to cold.
Elevation of diastolic, systolic, and mean blood pressures and cardiac hypertrophy occur in rats exposed to cold (5 degrees C) for 1-3 weeks. The renin-angiotensin-aldosterone system is believed to play a role in the development of cold-induced hypertension since plasma renin activity increases within the first 2 weeks, presumably initiating the hypertensive process, and then returns to control level. The present study was designed to assess the role of angiotension II (Ang II) in the hypertensive process by chronic administration of losartan potassium, an Ang II1 receptor antagonist. Twenty-four rats were divided into four equal groups. After a 1-week control period, one group was kept at 25 degrees C while the remaining three groups were exposed to cold (5 degrees C). One of the cold-treated groups was untreated while the remaining two were given losartan in drinking water at a concentration calculated to provide 56 and 112 mg/kg/day. The untreated cold-exposed group had a significant elevation of systolic blood pressure within 1 week of exposure to cold. Losartan at both doses prevented the elevation of blood pressure and blocked both the dipsogenic and vascular responses to administration of Ang II. Exposure to cold increased food intake, urine output and water intake significantly above that of warm-adapted controls. Treatment with losartan tended to decrease each of these toward the level of controls. At the conclusion of the seventh week of exposure to cold, the rats were sacrificed and heart, kidneys, and brown fat removed and weighed.(ABSTRACT TRUNCATED AT 250 WORDS)
Fregly
M J
MJ
Department of Physiology, University of Florida, College of Medicine, Gainesville 32610.
Rossi
F
F
Van Bergen
P
P
Brummermann
M
M
Cade
J R
JR
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002395:Catecholamines / Q000652:urine; D003080:Cold Temperature / Q000009:adverse effects; D004435:Eating / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D002395:Catecholamines; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan