Renal protective effects of chronic exercise and antihypertensive therapy in hypertensive rats with chronic renal failure.
OBJECTIVE
Patients with chronic renal failure are restricted to mild physical activity and tend to a lack of exercise. However, there have been few reports regarding the influence of chronic exercise on the progression of renal disease. Similarly, there are few animal models concerned with the effect of exercise training on improving renal function. Therefore, we assessed the renal effects of moderate chronic treadmill exercise in a remnant kidney model of spontaneously hypertensive rats (SHR) with chronic renal failure. We also assessed the effects of exercise and antihypertensive therapy on renal function.


METHODS
Eight-week-old SHR were subjected to 5/6 nephrectomy by removal of the left kidney and excision of two-thirds of the right kidney. The rats were divided into four groups: (i) no exercise (Non-EX); (ii) moderate exercise with treadmill running (20 m/min, 0 grade incline for 60 min) (EX); (iii) EX with an angiotensin converting enzyme (ACE) inhibitor, enalapril (2 mg/kg per day, i.p.); and (iv) EX with an angiotensin receptor antagonist, losartan (5 mg/kg per day, i.p.), for 4 weeks.


RESULTS
Chronic EX significantly attenuated the increase in proteinuria (P < 0.01) and significantly protected against increases in the index of glomerular sclerosis (IGS). Both enalapril and losartan with EX significantly decreased blood pressure (P < 0.001), and further decreased the IGS. In the stepwise multiple regression analysis, only antihypertensive drug remained in the model as a significant predictor of IGS (P < 0.0001). In contrast, exercise, antihypertensive drug and mean systolic blood pressure (weeks 1-4) remained in the model as a significant predictors of mean proteinuria (weeks 1-4) (all P < 0.0001).


CONCLUSIONS
These results suggest that exercise does not worsen renal function and has renal-protective effects in this model of rats. Moreover, the antihypertensive therapy has additional renal-protective effects in this model of rats.
Kohzuki
M
M
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan. kohzuki@mail.cc.tohoku.ac.jp
Kamimoto
M
M
Wu
X M
XM
Xu
H L
HL
Kawamura
T
T
Mori
N
N
Nagasaka
M
M
Kurosawa
H
H
Minami
N
N
Kanazawa
M
M
Saito
T
T
Yoshida
K
K
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004656:Enalapril / Q000494:pharmacology; D006973:Hypertension / Q000150:complications* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000503:physiopathology*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009043:Motor Activity; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; D019808:Losartan