Chronic and acute effects of different antihypertensive drugs on femoral artery relaxation of L-NAME hypertensive rats.
We aimed to compare the effects of chronic and acute administration of structurally different antihypertensives, diuretics - indapamide and hydrochlorothiazide, ACE inhibitor - captopril and indapamide+captopril combination on endothelium-dependent relaxation of femoral artery isolated from nitric oxide (NO)-deficient rats. In the chronic experiment, femoral artery was isolated from Wistar rats receiving L-NAME (40 mg/kg/day) solely or with indapamide (1 mg/kg/day), hydrochlorothiazide (10 mg/kg/day), captopril (10 mg/kg/day), and indapamide+captopril combination for seven weeks. In the acute in vitro experiment, the incubation medium with femoral artery isolated from L-NAME-hypertensive rats was supplemented with investigated antihypertensives in the same concentration 10(-4) mol/l. Interestingly, chronic L-NAME treatment did not cause a reduction of vasorelaxation. Indapamide+captopril elevated relaxation above the control level and completely prevented blood pressure increase induced by L-NAME. Acute incubation with captopril only or indapamide+captopril improved relaxation of femoral artery isolated from L-NAME-hypertensive rats, while the incubation with all antihypertensives increased vasorelaxation of femoral artery isolated from control Wistar rats. In conclusion, NO might be involved in the indapamide- and hydrochlorothiazide-induced improvement of vasorelaxation, while different vasorelaxing factors (prostacyclin, EDHF) contribute to the captopril-induced improvement of vasorelaxation. During the chronic treatment additive and synergic effects of indapamide and captopril may contribute to the prevention of hypertension and increase of vasorelaxation.
Sládková
M
M
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Kojsová
S
S
Jendeková
L
L
Pechánová
O
O
D000109:Acetylcholine / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology; D004334:Drug Administration Schedule; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005263:Femoral Artery / Q000187:drug effects* / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D007190:Indapamide / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology