Drug-Induced Alteration of Endothelial Permeability in the Rat Aorta

Abstract

We recently reported that some diuretics affect capillary permeability in the normotensive rat. In the present study, we explore the effect of selected antihypertensive drugs administered orally during 10 days, on Evans blue (EB) extravasation within the wall of the thoracic (TA) and abdominal aorta (AA) obtained from spontaneously hyertensive rats (SHR). Description of the EB method has been previously reported. Daily doses (mg/kg) of captopril (CAP: 3.0), perindopril (PER: 0.3), nifedipine (NIF: 1.0), clentiazem (CLE: 0.1), hydralazine (HYD: 0.5), furosemide (FUR: 0.5), cicletanine (CIC: 2.0), hydrochlorothiazide (HCZ: 0.5), and indapamide (IND: 0.04) resulted in comparable blood pressure reduction. Percent changes in EB tissue concentration (measured in ug/g dry tissue) was increased by 24% in both the TA and AA in the untreated SHR. CAP reduced by half EB leakage in the TA, while PER decreased EB extravasation 16% below baseline values. Both angiotensin converting enzyme inhibitors failed to normalize EB leakage in the AA. The calcium channel blockers also normalized EB extravasation in the two segments of the aorta, except that CLE was without effect in the AA. HYD normalized EB leakage in the TA, but not in the AA. All diuretics tested reduced EB extravasation by 48 to 58% below baseline values in the TA, whereas CIC only normalized EB leakage. None of the diuretics affected EB extravasation in the AA of the SHR. In conclusion: 1- the two segments of the aorta were similarly affected in the SHR; 2- despite comparable effect on blood pressure, treatment of the SHR was associated with different responses in the TA and AA; 3- within a given class of drugs, different effects are observed on EB.