NEW DIHYDROPYRIDINE CALCIUM-CHANNEL ANTAGONIST, PRANIDIPINE, ATTENUATES HYPERTENSIVE RENAL INJURY IN DAHL SALT-SENSITIVE RATS

Interest in the cardiovascular protective effects of calcium channel a ntagonists has increased in the past decade. We investigated preventio n of vascular wall remodeling by the long-acting calcium channel antag onist pranidipine in 12-week-old Dahl salt-sensitive (SS) rats with hi gh-salt-induced (4% NaCl) hypertension. Six-week pranidipine treatment (60 mg/kg chow) decreased systolic blood pressure (SBP) by 22% in SS rats. This BP reduction was associated with decreases in cardiac mass and weight of the aortic wall. Glomerular filtration rate (GFR) was in creased by 33%, but this did not lead to a decrease in urinary protein or NAG excretion. Morphologic investigation demonstrated striking res olution of arterial injury (medial necrosis and/or hyperplasia, inflam matory cell infiltration, and thrombus formation) by 87% after pranidi pine treatment. Glomerular sclerosis was also attenuated by 61%, where as tubular injury was improved by only 28%. These morphologic changes were reflected in the findings that the capacity of kidney homogenate for generating lipid peroxides was significantly decreased and that co llagen levels and pattern type became similar to those of normotensive salt-resistant (SR) rats. Pranidipine also attenuated hypertensive va sculopathy in small arteries of the middle cerebral arteries. Thus, th e calcium channel antagonist pranidipine can attenuate the vascular in jury that occurs in salt-induced hypertension, a promising property th at implicates its clinical usage, particularly in essential hypertensi on with cardiovascular complications.