Effects of indapamide on the mechanical properties of the arterial wall in deoxycorticosterone acetate-salt hypertensive rats

Abstract

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) (μl/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. In contrast, systemic arterial compliance was significantly increased by treatment with indapamide in the hypertensive group. Furthermore, there were significant differences in CC (mean ± standard error of the mean) measured in Wistar and DOCA-salt animals. Maximal values of CC measured for pressure values close to the operating pressures in both groups were higher in the untreated DOCA-salt group than in the normotensive Wistar group (0.17 ± 0.02 and 0.14 ± 0.01 μl/mm Hg, respectively, p < 0.001). Maximal values of CC were increased by 32 and 30% after KCN poisoning in Wistar and DOCA-salt rats, respectively (p < 0.01). The treatment by indapamide induced a significant increase in CC both in the normotensive and hypertensive groups (+18 and +30%, respectively, p < 0.01). Although there was a reserve of CC in Wistar rats pretreated with indapamide (significant decrease in stiffness after KCN poisoning), there was no further increase in CC in hypertensive rats when KCN poisoning was performed after treatment with indapamide. These results suggest that (1) in the first weeks of hypertension induced by DOCA and salt diet, a significant decrease occurred in arterial stiffness possibly related to modifications in vascular connective tissues and in arterial vascular smooth muscle tone; and (2) acute treatment with indapamide induced an increase in arterial compliance in both normotensive and hypertensive rats.