The renin-angiotensin and adrenergic nervous system in cardiac hypertrophy in fructose-fed rats.
BACKGROUND
Hyperinsulinemia and insulin resistance are associated with left ventricular hypertrophy (LVH) and cardiovascular complications in hypertensive subjects. The aim of this study was to explore the mechanisms for LVH including activation of the renin-angiotensin system system (RAS) and the sympathetic nervous system and their activation by insulin using a rat model of hyperinsulinemia and insulin resistance.


METHODS
Male Sprague-Dawley rats were fed a high-fructose or control diet. The fructose-fed rats (FFR) were divided into four subgroups that were administrated either vehicle or the following antihypertensive drugs (n = 6-8) for 4 weeks: 1) olmesartan, an angiotensin II type 1 (AT1) receptor antagonist; 2) bunazosin, an alpha1-receptor blocker; and 3) hydralazine, a direct vasodilator.


RESULTS
Fructose feeding induced significant increases in mean systolic blood pressure (BP) levels at 4 weeks (control, 117 v fructose, 131 mm Hg), left ventricular weight, and the sum of the insulin level in response to a glucose tolerance test (2 g/kg). Fructose feeding also increased urinary excretion of epinephrine and norepinephrine, the density of cardiac alpha1-adrenergic receptors, and the content of angiotensin II in the left ventricle. All antihypertensive drugs decreased systolic BP, but only the AT1 receptor antagonist attenuated the development of LVH in FFR. The AT1 receptor antagonist did not affect glucose-mediated insulin responses, but did suppress urinary catecholamine excretion and cardiac alpha1-adrenergic receptor density.


CONCLUSIONS
Left ventricular hypertrophy in FFR may be less dependent on systemic elevations of BP and more dependent on the RAS and the sympathetic nervous system. Use of an AT1 receptor antagonist might be the most beneficial way to prevent progression of LVH through direct effects on tissue RAS and the sympathetic nervous system in FFR. As these changes occur in a rat model with hyperinsulinemia, insulin may have a role in promoting LVH by activating the local RAS and sympathetic nervous system activity.
Kamide
Kei
K
Department of Geriatric Medicine, Osaka University Medical School, Suita, Japan.
Rakugi
Hiromi
H
Higaki
Jitsuo
J
Okamura
Atsunori
A
Nagai
Michiko
M
Moriguchi
Kouichi
K
Ohishi
Mitsuru
M
Satoh
Noriyuki
N
Tuck
Michael L
ML
Ogihara
Toshio
T
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002395:Catecholamines / Q000652:urine; D004032:Diet; D005632:Fructose / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006830:Hydralazine / Q000494:pharmacology; D006946:Hyperinsulinism / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000473:pathology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D000068557:Olmesartan Medoxomil; D009929:Organ Size; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000959:Antihypertensive Agents; D001786:Blood Glucose; D002395:Catecholamines; D007093:Imidazoles; D007328:Insulin; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; D005632:Fructose; D000068557:Olmesartan Medoxomil; C018176:bunazosin