Effects of Losartan on Blood Pressure, Metabolic Alterations, and Vascular Reactivity in the Fructose-Induced Hypertensive Rat

Abstract

Fructose feeding induces a moderate increase in blood pressure levels in normal rats that is associated with insulin resistance, hyperinsulinemia, and hypertriglyceridemia. The sympathetic nervous system seems to participate in the alterations of this model. To further explore the mechanisms underlying fructose-induced hypertension, the effects of the AT1 receptor antagonist losartan on blood pressure, insulin resistance, renal function, and vascular reactivity in mesenteric vascular beds were studied. Sprague-Dawley rats were fed for 4 weeks with diets containing 60% fructose or 60% starch (control), and half of each group received losartan (1 mg/kg per day) in the drinking water. Fructose-fed rats showed higher (P < .05) blood pressure levels and plasma concentrations of triglycerides and insulin than those of controls. Losartan treatment prevented both blood pressure elevation and hyperinsulinemia in fructose-fed rats but not elevation of plasma triglycerides. Plasma glucose and insulin levels in response to an oral glucose load were higher (P < .05) in fructose-fed rats than in controls. These exaggerated responses were prevented by losartan treatment. No differences in the constrictor responses of mesenteric vascular beds to KCl (60 mumol), angiotensin II (1 nmol), phenylephrine (10(-5) mol/L), or endothelin-1 (10 pmol) were found between the two groups. Relaxing responses to acetylcholine or sodium nitroprusside in phenylephrine-precontracted mesenteric vascular beds and constrictor response to the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (100 nmol) were comparable in both groups. Losartan blunted angiotensin II constriction and reduced (P < .05) responses to phenylephrine in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Angiotensin II Receptor Antagonists on Insulin Resistance Syndrome and Leptin in Sucrose-Fed Spontaneously Hypertensive Rats.

“…Additionally, it has been reported that sucrose feeding increases norepinephrine excretion, turnover, and plasma concentration and enhances sympathetic nerve responses in rats (26,27). Thus sympathetic overactivity may be involved in the pathogenesis of this model, and may be responsible at least in part for the impairment of blood flow to skeletal muscle, which in turn would favor the development of insulin resistance (28). The finding that Fig.…”

“…Such locally generated angiotensin II could induce peripheral vasoconstriction, and could contribute to blood pressure elevation and insulin resistance. Consequently, it is possible that ARA exerts its beneficial effects by the suppression of the vascular actions of angiotensin II via AT1 receptor antagonism (28). This would reduce elevated blood pressure levels and restore a normal flow to the skeletal muscle, which would facilitate glucose uptake.…”

Mecanismos Fisiológicos E Fisiopatológicos Determinantes Da Atividade Vasomotora Simpática

“…Além disso, há importante participação da Ang II. Estes resultados confirmam evidências anteriores da literatura nas quais, o bloqueio farmacológico do SRAA por inibidores da enzima conversora de angiotensina ou por antagonistas de receptores AT 1 foi capaz de normalizar a PA bem como a captação periférica de glicose 64,65 . Neste modelo, a hiperinsulinemia parece também desempenhar papel importante no desencadeamento da hiperatividade simpática uma vez que, em ratos, demonstrou-se, nestas condições, ativação simpática para diferentes tecidos, incluindo o renal 66 .…”

Fibrotic response to angiotensin II is blunted in the kidney, but not in the heart, in insulin-sensitive long-lived transgenic dwarf rats

“…Furthermore, renal cell growth and extracellular matrix (ECM) synthesis and degradation were modulated by Ang II, leading to glomerulosclerosis and interstitial fibrosis and consequently to advanced renal failure (8). It has also been shown that ACE inhibitor and the Ang II receptor blocker improve insulin sensitivity and reduce blood pressure in essential hypertension and fructose-induced hyperinsulinemic hypertensive rats (9)(10)(11). However, it is not clear whether a blunted response to Ang II is found in insulinsensitive animal models.…”