Effects of antihypertensive drugs and exercise training on insulin sensitivity in spontaneously hypertensive rats.
We examined the effects of antihypertensive drugs, exercise training, and combinations thereof on insulin sensitivity (IS), and the association between this relation and sympathetic activity, muscle fiber composition, and capillary density in spontaneously hypertensive rats (SHR). Six-week-old male SHR were allocated to 7 groups: a control group (C), and groups treated with azelnidipine (Aze) (a calcium channel blocker), olmesartan (Olm) (an angiotensin II type 1 receptor blocker), exercise training (Exe), and combinations of drugs and exercise training (Aze+Exe, Olm+Exe, and Olm+Aze+Exe). At age 18 weeks, IS and sympathetic activity were evaluated by an euglycemic hyperinsulinemic glucose clamp technique and power spectral analysis of systolic blood pressure, respectively. After the experiments, capillary density and muscle fiber composition in soleus muscle were examined. Aze or Exe alone significantly increased IS associated with a significant reduction in sympathetic activity. Olm alone tended to increase IS with little change in sympathetic activity. Aze, Olm, or Exe significantly increased the capillary density and percentage of insulin-sensitive type I fiber. A combination of Aze and Exe or a combination of Olm and Exe tended to increase IS compared with each drug therapy alone. There were significant correlations between IS and sympathetic activity, capillary density, and the percentage of type I fiber in all the rats. We found that Aze improved IS more substantially compared with Olm in SHR. We also found that Aze, Olm, Exe, and combinations thereof improved IS, probably through the modulation of sympathetic activity or capillarity and muscle fiber type in skeletal muscles.
Guo
Qi
Q
Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
Minami
Naoyoshi
N
Mori
Nobuyoshi
N
Nagasaka
Makoto
M
Ito
Osamu
O
Kurosawa
Hajime
H
Kanazawa
Masayuki
M
Kohzuki
Masahiro
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003131:Combined Modality Therapy; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology* / Q000628:therapy; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D012044:Regression Analysis; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D013777:Tetrazoles / Q000494:pharmacology* / Q000627:therapeutic use
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D007093:Imidazoles; D007328:Insulin; D013777:Tetrazoles; D001383:Azetidinecarboxylic Acid; C437965:olmesartan; C061679:azelnidipine