Effects of chronic losartan treatment on vascular reactivity in normotensive rats.
OBJECTIVE
To investigate the vasoactive properties of large (aorta) and small (mesenteric) arteries in vitro after chronic losartan treatment of normotensive rats, hence providing information on the role played by angiotensin II in vascular tone.


METHODS
Wistar rats were treated with 10 mg/kg per day losartan for 3 weeks. Ring segments of thoracic aorta and mesenteric resistance arteries (200 microns diameter) were mounted in myographs and wall force measured isometrically.


RESULTS
The mean carotid blood pressure was reduced significantly after chronic losartan treatment (108 +/- 3 mmHg, n = 17 versus 116 +/- 2 mmHg, n = 16 in control rats, P < 0.05). In the mesenteric resistance artery the contractile response to 125 mmol/l K+, phenylephrine and angiotensin II was not affected significantly by losartan treatment. A subcontractile concentration of angiotensin II (0.1 nmol/l) induced a significant potentiation of the response to 0.03-100 mumol/l) phenylephrine (450 +/- 180 to 150 +/- 20% of the previous response to phenylephrine in control rats). This potentiation was attenuated significantly in the losartan group (240 +/- 80 to 100 +/- 15% of the previous response, P < 0.01 versus control rats). In the aorta, the response to 125 mmol/l K+ was not affected by chronic losartan treatment. The concentration required for the half-maximal effect for phenylephrine was increased significantly in the losartan group (0.51 +/- 0.11 mumol/l versus 0.17 +/- 0.03 mumol/l in controls rats; no change in maximum response) and the maximum response to angiotensin II was reduced significantly (0.7 +/- 0.08 mN/mg tissue versus 1.9 +/- 0.2 mN/mg tissue in control rats; the concentration for the half-maximal effect was not affected). Potentiation of phenylephrine-induced tone by 0.1 nmol/l angiotensin II (273 +/- 55 to 122 +/- 12% of the previous response in control rats) was attenuated significantly by losartan treatment (91 +/- 46 to 95 +/0 23% of the previous response, P < 0.01 versus control)


CONCLUSIONS
Chronic administration of losartan could act on resistance arteries in normotensive rats by blocking the potentiation by angiotensin II of the agonist-induced tone.
Dowell
F J
FJ
Institut National de la Santé et de la Recherche Médicale (INSERM) U 141, Paris, France.
Benessiano
J
J
Poitevin
P
P
Levy
B I
BI
Henrion
D
D
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004347:Drug Interactions; D007093:Imidazoles / Q000008:administration & dosage*; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000008:administration & dosage*; D014661:Vasoconstriction / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D000804:Angiotensin II; D010656:Phenylephrine; D019808:Losartan; D011188:Potassium