New dihydropyridine calcium channel antagonist, pranidipine, attenuates hypertensive renal injury in Dahl salt-sensitive rats.
Interest in the cardiovascular protective effects of calcium channel antagonists has increased in the past decade. We investigated prevention of vascular wall remodeling by the long-acting calcium channel antagonist pranidipine in 12-week-old Dahl salt-sensitive (SS) rats with high-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 increased by 33%, but this did not lead to a decrease in urinary protein or NAG excretion. Morphologic investigation demonstrated striking resolution of arterial injury (medial necrosis and/or hyperplasia, inflammatory cell infiltration, and thrombus formation) by 87% after pranidipine treatment. Glomerular sclerosis was also attenuated by 61%, whereas 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 collagen levels and pattern type became similar to those of normotensive salt-resistant (SR) rats. Pranidipine also attenuated hypertensive vasculopathy in small arteries of the middle cerebral arteries. Thus, the calcium channel antagonist pranidipine can attenuate the vascular injury that occurs in salt-induced hypertension, a promising property that implicates its clinical usage, particularly in essential hypertension with cardiovascular complications.
Uehara
Y
Y
2nd Department of Medicine, University of Tokyo, Japan.
Kawabata
Y
Y
Ohshima
N
N
Hirawa
N
N
Takada
S
S
Numabe
A
A
Nagata
T
T
Goto
A
A
Yagi
S
S
Omata
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control*; D008954:Models, Biological; D011188:Potassium / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood; D012982:Sodium, Dietary / Q000009:adverse effects
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D012982:Sodium, Dietary; C048161:pranidipine; D012964:Sodium; D011188:Potassium