Effects of indapamide on the mechanical properties of the arterial wall in deoxycorticosterone acetate-salt hypertensive rats.
An experimental model of "in situ" isolated carotid artery has been used to evaluate the static mechanical properties of the arterial wall in 12-week-old Wistar and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The rats were made hypertensive by left kidney removal, DOCA (50 mg) tablet implantation for 2 weeks, and saline diet (NaCl 9% solution as beverage). Normotensive control rats (n = 24) and DOCA-salt hypertensive rats (n = 24) received indapamide, 10 mg/kg, or placebo by gavage 12 hours and 1 hour before measurements were obtained. The rats were anesthetized (pentobarbital 50 mg/kg), intubated and ventilated, and a midsternal thoracotomy was performed. A first catheter was introduced into the ascending aorta through the right carotid artery. A perivascular ultrasonic flow probe was placed around the ascending aorta and allowing simultaneous recording of the phasic ascending aortic pressure and flow. Systolic and diastolic pressure, cardiac output and heart rate were directly measured. Peripheral resistance and systemic arterial compliance were calculated from hemodynamic records. After hemodynamic measurements, a segment of the left carotid artery was then isolated in vivo and its volume-pressure relationship was recorded before and 30 minutes after total abolition of the vascular muscle tone by local incubation with a potassium cyanide solution (KCN) (100 mg/liter) for pressures ranging from 50 to 175 mm Hg. The carotid compliance (CC) (microliter/mm Hg) was calculated, for every pressure step, as the slope of the volume-pressure curves. Indapamide significantly reduced the arterial pressure in hypertensive rats, and this was related to a marked decrease in total peripheral resistance. Heart rate was not modified by indapamide.(ABSTRACT TRUNCATED AT 250 WORDS)
Levy
B I
BI
Institut National de la Santé et de la Recherche Médicale, Hôpital Lariboisière, Paris, France.
Poitevin
P
P
Safar
M E
ME
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects*; D003900:Desoxycorticosterone / Q000009:adverse effects / Q000031:analogs & derivatives; D004232:Diuretics / Q000494:pharmacology*; D004548:Elasticity; D006973:Hypertension / Q000503:physiopathology*; D007190:Indapamide / Q000494:pharmacology*; D010919:Placebos; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D004232:Diuretics; D010919:Placebos; D003900:Desoxycorticosterone; D007190:Indapamide