DIFFERENT EFFECTS OF CALCIUM-ANTAGONISTS ON FLUID FILTRATION OF LARGEARTERIES AND ALBUMIN PERMEABILITY IN SPONTANEOUSLY HYPERTENSIVE RATS

Objective To compare the effects of chronic administration of two dihy dropyridines, nifedipine and amlodipine, and the non-dihydropyridine C a2+ antagonist mibefradil on fluid filtration of large arteries and ex travasation of albumin in spontaneously hypertensive rats. Methods Spo ntaneously hypertensive rats aged 2 months were randomly allocated to oral treatment once a day with 30 mg/kg mibefradil (n = 12), 100 mg/kg nifedipine (n = 12), 20 mg/kg amlodipine (n = 12) or placebo (n = 12) for 1 month. Instantaneous blood pressure of rats under pentobarbital anaesthesia was recorded at the end of the treatment. Fluid filtratio n across the carotid arterial wall was determined in situ in the isola ted carotid artery. Extravasation of 25 mg/kg Evans Blue dye that had been injected intravenously was used to assess whole vascular permeabi lity to albumin after chronic treatment with mibefradil. Results Simil ar reductions in mean arterial pressure were obtained in all Ca2+ anta gonist-treated rats. Heart rate was similar in rats in control, nifedi pine and amlodipine groups but was significantly lower in mibefradil-t reated rats (by 19%, P < 0.001). Fluid filtration across the carotid w all was greater in all Ca2+ antagonist-treated animals. However, fluid filtration was significantly less in mibefradil-treated rats than it was in nifedipine-treated, and amlodipine-treated rats. Furthermore, a dministration of mibefradil did not significantly modify extravasation of albumin in all tested tissues (pancreas, testis, spleen, lung, kid ney, intestine, liver, skeletal muscle) except for cardiac and brain t issues, in which the permeability of albumin was increased by 24 and 3 3%, respectively, compared with values for the control group (P < 0.05 ). Conclusion These results indicate that Ca2+ antagonists increase fl uid filtration through large arteries from spontaneously hypertensive rats. That the lower fluid filtration in mibefradil-treated rats was a ssociated with no change in extravasation of albumin in most tissues a nd especially in skeletal muscle suggests that vascular permeability i n hypertensive rats was impaired less by mibefradil treatment than it was by dihydropyridine Ca2+ antagonist treatments. (C) 1998 Rapid Scie nce Ltd.