Detrimental Impact of Vasopressin V2 Receptor Antagonism in a SU5416/Hypoxia/Normoxia-Exposed Rat Model of Pulmonary Arterial Hypertension

Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload

“…In another experiment, almost 25% of rats died during the first 5 weeks of SU5416 injection by using the same experimental method [108]. Other studies have shown that the same results can be seen at 8 and 9 weeks after hypoxia treatment [106,107].…”

“…Taraseviciene-Stewart et al demonstrated for the first time that SU5416 combined with chronic hypoxia could result in severe pulmonary hypertension and pulmonary vascular remodeling [103]. Most researchers reported changes in pulmonary blood vessels and myocardium at 3 weeks of SU5416 injection (20 mg/kg) and 10% O 2 exposure [104][105][106][107]. One study showed that early fibrosis was first detected at 5 weeks (exposure to hypoxic state for 3 weeks and normoxic state for 2 weeks) in SU5416 rats, and, at the cellular level, the signs of cardiomyocyte degeneration appeared, along with various degrees of collagen deposition [105].…”

Novel molecular mechanisms in the inhibition of adrenal aldosterone synthesis: Action of tolvaptan via vasopressin V2 receptor‐independent pathway

“…In the tolvaptan and AngII + tolvaptan groups, 0.05% tolvaptan in the diet was started 24 hr after the initiation of AngII infusion, because the pumping of AngII started approximately 24 hr after implantation (Lu et al, 2015). This dose of tolvaptan was chosen from our recent (Goto et al, 2016) and previous (Morooka et al, 2012) studies. Then the rats of all four groups were individually placed into the metabolic cages, where they had free access to food and water, for the assessment of fluid and food intake and urine volume for 24 hr.…”

“…Importantly, several experimental (Miyazaki, Fujiki, Yamamura, Nakamura, & Mori, 2007) and clinical studies (Boerrigter et al, 2006;Jujo et al, 2016) have reported that tolvaptan therapy avoids RAAS activation despite its strong diuretic effect in HF. A recent experimental study in our laboratory has demonstrated that chronic tolvaptan therapy suppressed plasma aldosterone level in a rat model of pulmonary arterial hypertension (Goto et al, 2016). However, the precise effect of tolvaptan on the RAAS, especially under pathological conditions in which the adrenals produce more aldosterone in response to AngII, is not established.…”

“…Several experimental and clinical trials have shown the effectiveness of tolvaptan for improving symptoms and decreasing body fluids in HF patients. A recent experimental study in our laboratory has demonstrated that chronic tolvaptan therapy suppressed plasma aldosterone level in a rat model of pulmonary arterial hypertension (Goto et al, 2016). A recent experimental study in our laboratory has demonstrated that chronic tolvaptan therapy suppressed plasma aldosterone level in a rat model of pulmonary arterial hypertension (Goto et al, 2016).…”