RESUMEN
PURPOSE: Hypertension is one of the major risk factors for renal failure and cardiovascular diseases, and is caused by various abnormalities including the contractility of blood vessels. Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which mimic human type 2 diabetes, are frequently used to study obesity-induced insulin resistance (IR) and hypertension. Human omentin-1 is one of the recently identified adipocytokines. We previously demonstrated that human omentin-1 not only caused vasodilation in rat isolated blood vessels, but also prevented inflammatory responses, a possible mechanism relating IR, in human vascular endothelial cells. Taken together, we hypothesized that human omentin-1 may reduce obesity-induced IR and hypertension in OLETF rats. METHODS: OLETF rats were intraperitoneally administered with human omentin-1 for 7 days. RESULTS: Human omentin-1 had no influence on overweight, hyperglycemia, urinary glucose extraction, hyperinsulinemia, and systemic IR in OLETF rats. Human omentin-1 decreased systolic blood pressure in OLETF rats. The measurement of isometric contraction revealed that human omentin-1 had no influence on the agonist-induced contractile and relaxant responses in isolated thoracic aorta from OLETF rats. However, the relaxant response mediated by human insulin was converted into the contractile response in thoracic aorta from OLETF rats, which was prevented by human omentin-1. The Western blotting revealed that human omentin-1 improved the decrease in endothelial nitric oxide synthase activation in isolated thoracic aorta from OLETF rats. CONCLUSION: In summary, we for the first time revealed that human omentin-1 partly reduces vascular IR and thereby inhibits hypertension in OLETF rats.
RESUMEN
Soluble guanylate cyclase (sGC) stimulator riociguat is a relatively novel therapeutic agent for pulmonary hypertension (PH) in human medicine. Riociguat induces endothelium-independent pulmonary artery (PA) relaxation by directly activating the sGC-cyclic guanosine-3',5'-monophosphate (cGMP) pathway in muscle cells. Although riociguat may be effective in the treatment of dogs with refractory PH, basic studies on its clinical application in veterinary medicine are lacking. The present study aimed to explore the effects of riociguat on the contractility of an isolated canine PA and the hemodynamics of dogs with acute PH. In an isolated endothelium-denuded canine PA, the effects of riociguat on endothelin (ET)-1-induced contraction and cGMP levels were investigated using the Magnus method and ELISA, respectively. The effect of riociguat on the hemodynamics of the thromboxane A2 analog U46619-induced PH model dog was examined by invasive catheterization. Riociguat increased cGMP levels and reduced ET-1-induced contraction of the isolated PA. Riociguat inhibited the U46619-induced elevation of PA pressure and pulmonary vascular resistance and increased cardiac output, but it had no effect on basal systemic blood pressure. These results demonstrate for the first time that riociguat can inhibit the elevation of PA pressure through PA relaxation via an endothelium-independent increase in cGMP in dogs with PH.
RESUMEN
Hypertension is one of the major risk factors for cardiovascular diseases and is caused by various abnormalities including the contractility of blood vessels. Spontaneously hypertensive rats (SHR), whose systemic blood pressure increases with aging, are a frequently used animal model for investigating essential hypertension and related complications in humans due to the damage of several organs. Human omentin-1 is an adipocytokine consisting of 313 amino acids. Serum omentin-1 levels decreased in hypertensive patients compared with normotensive controls. Furthermore, omentin-1 knockout mice showed elevated blood pressure and impaired endothelial vasodilation. Taken together, we hypothesized that adipocytokine, human omentin-1 may improve the hypertension and its complications including heart and renal failure in the aged SHR (65-68-weeks-old). SHR were subcutaneously administered with human omentin-1 (18 µg/kg/day, 2 weeks). Human omentin-1 had no effect on body weight, heart rate, and systolic blood pressure in SHR. The measurement of isometric contraction revealed that human omentin-1 had no influence on the enhanced vasocontractile or impaired vasodilator responses in the isolated thoracic aorta from SHR. On the other hand, human omentin-1 tended to improve left ventricular diastolic failure and renal failure in SHR. In summary, human omentin-1 tended to improve hypertensive complications (heart and renal failure), while it had no influence on the severe hypertension in the aged SHR. The further study of human omentin-1 may lead to the development of therapeutic agents for hypertensive complications.
