Cardiorenal protective effects of year-long antihypertensive therapy with an angiotensin-converting enzyme inhibitor or a calcium channel blocker in spontaneously hypertensive rats.
BACKGROUND
The objective of this study was to evaluate the effect of year-long antihypertensive therapy with a calcium channel blocker and an angiotensin-converting enzyme (ACE) inhibitor on cardiac and renal injury.


METHODS
Male 15-week-old spontaneously hypertensive rats (SHR) were given either a normal diet and normal drinking water (n = 10), a diet containing 0.05% nitrendipine (n = 10), or drinking water containing 50 mg/L of quinapril (n = 10). After 12 months of antihypertensive treatment, cardiovascular organ injuries were evaluated.


RESULTS
Tail-cuff blood pressure (BP) at 12 months was significantly lower in animals receiving nitrendipine or quinapril than in control animals (control, 231 +/- 2 mm Hg; nitrendipine, 194 +/- 3 mm Hg; quinapril, 191 +/- 3 mm Hg; P < .001). Furthermore, aortic thickness was reduced by nitrendipine (-19%, P < .001) or quinapril (-21%, P < .001), and cardiac ventricular weight was significantly reduced by quinapril (-18%, P < .001) but not by nitrendipine (-5%, P = not significant [NS]). Echocardiography at 12 months revealed that midwall fractional shortening was higher in the quinapril group than in the control or the nitrendipine groups (control, 9.3% +/- 0.5%; nitrendipine, 9.8% +/- 0.5%; quinapril, 10.6% +/- 0.6%; P < .05). Left ventricular hydroxyproline levels were lower in the nitrendipine group (-21%, P < .01) and the quinapril group (-36%, P < .001) than in the control animals. In control SHR, creatinine clearance began to decrease and proteinuria began to increase at 6 to 9 months. Quinapril but not nitrendipine attenuated these markers of renal impairment (creatinine clearance at 12 months: control, 4.7 +/- 0.4 mL/min/kg; nitrendipine, 5.0 +/- 0.4 mL/min/kg; quinapril, 6.1 +/- 0.4 mL/min/kg; P < .05). Histologically, the glomerular injury score was lower in the quinapril group than in the control or nitrendipine groups (control, 19 [range, 8 to 30]; nitrendipine, 18 [range, 9 to 32]; quinapril, 7 [range, 3 to 12]; P < .01).


CONCLUSIONS
It is suggested that year-long antihypertensive therapy with an angiotensin-converting enzyme (ACE) inhibitor is superior to a calcium channel blocker in terms of cardiorenal protection in SHR.
Ishimitsu
Toshihiko
T
Department of Hypetension and Cardiorenal Medicine, Dokkyo Medical University, Mibu, Tochigi, Japan. isimitu@dokkyomed.ac.jp
Honda
Takeaki
T
Ohta
Satoshi
S
Akashiba
Akira
A
Takahashi
Toshiaki
T
Kameda
Tomoko
T
Yoshii
Masayoshi
M
Minami
Junichi
J
Takahashi
Masaki
M
Ono
Hidehiko
H
Matsuoka
Hiroaki
H
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011507:Proteinuria / Q000517:prevention & control; D000077583:Quinapril; D051381:Rats; D011918:Rats, Inbred SHR; D044005:Tetrahydroisoquinolines / Q000494:pharmacology; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D044005:Tetrahydroisoquinolines; D009568:Nitrendipine; D000077583:Quinapril