The role of renal natriuretic and depressor systems in insulin-resistant hypertensive rats.
Insulin resistance and impairment of the renal depressor system have been thought to be involved in the development of essential hypertension. However, the relationship between insulin resistance and this system is still unclear. To clarify this relationship, we investigated the role of the renal depressor system in a rat model of insulin-resistant hypertension. Sprague-Dawley rats were fed a standard diet (control) or a fructose-rich diet (FFR), and their blood pressures were measured every week. Urinary dopamine (uDA), urinary kallikrein (uKAL) activity and urinary nitric oxide (uNOx) levels were also measured each week, and the renal mRNA expression levels of endothelial nitric oxide synthase (eNOS), aromatic-L-amino-acid decarboxylase (AADC), and kallikrein (KAL) activity were compared at the end of the study. The blood pressure of FFR was elevated significantly from 2 weeks after the start of fructose loading. The uDA level was lower in FFR than in control rats throughout the study period (p<0.01), and the expression level of AADC mRNA was enhanced in FFR (p<0.05). There was a tendency of negative correlation between uDA level and systolic blood pressure (SBP) (r=-0.49, p=0.056). uNOx level was lower in FFR throughout the study period (p<0.05), and the eNOS mRNA expression level in the kidney was lower in FFR than in control rats (p<0.05). There was a negative correlation between uNOx level and SBP (r=-0.68, p <0.01). On the other hand, there was no significant difference in the kallikrein-kinin system between FFR and control rats. In conclusion, impairment in functions of the renal dopamine and NO systems occur in FFR, and this impairment may be caused by insulin resistance and may contribute to the development of hypertension.
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Japan. khasegaw@sapmed.ac.jp
Koichi
K
Hasegawa
Hideaki
H
Yoshida
Nobuyuki
N
Ura
Hideyuki
H
Murakami
Makoto
M
Hagiwara
Kazuaki
K
Shimamoto
D000818:Animals; D004298:Dopamine / Q000652:urine*; D006973:Hypertension / Q000503:physiopathology* / Q000652:urine; D007333:Insulin Resistance; D007610:Kallikreins / Q000652:urine*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000652:urine*; D009573:Nitrites / Q000652:urine*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009566:Nitrates; D009573:Nitrites; D007610:Kallikreins; D004298:Dopamine