Takashi Kometani

Prophylactic effects of elastin peptide derived from the bulbus arteriosus of fish on vascular dysfunction in spontaneously hypertensive rats.

AIMS To determine the prophylactic effects of an elastin peptide derived from the bulbus arteriosus of bonitos and prolylglycine (PG), a degradation product of elastin peptide, on vascular dysfunction in spontaneously hypertensive rats (SHRs). MAIN METHODS Male 15-week-old SHR/Izm rats were fed without (control group) or with elastin peptide (1 g/kg body weight) for 5 weeks (EP group), or were infused via an osmotic mini-pump for 4 weeks with PG (PG group) or saline (control group). Using thoracic aortas, we assessed endothelial changes by scanning electron microscopy. Vascular reactivity (contraction and relaxation) and pressure-induced distension was compared. mRNA production levels of endothelial nitric oxide synthase (eNOS) and intercellular adhesion molecule-1 (ICAM-1) were investigated by real-time-polymerase chain reaction. KEY FINDINGS Aortas of the EP group displayed limited endothelial damage compared with that in the control group. Under treatment of SHRs with elastin peptide, the effect of phenylephrine returned closer to the normal level observed in normotensive Wistar-Kyoto (WKY/Izm) rats. mRNA production of eNOS (but not ICAM-1) was greater in the EP group than in the control group. Endothelial damage was suppressed and pressure-induced vascular distension was greater in the PG group than in the corresponding control group. SIGNIFICANCE These results suggest that elastin peptide from bonitos elicits prophylactic affects hypertension-associated vascular dysfunction by targeting the eNOS signaling pathway. PG may be a key mediator of the beneficial effects of elastin peptide.

Heart‐bound adiponectin, not serum adiponectin, inversely correlates with cardiac hypertrophy in stroke‐prone spontaneously hypertensive rats

What is the central question of this study? An inverse correlation between circulating adiponectin and many diseases has been reported, but some studies have found no correlation. To evaluate this controversy, we investigated the relationship between heart‐bound adiponectin and hypertension or cardiac hypertrophy, compared with serum adiponectin. What is the main finding and its importance? Using hypertensive and normotensive rats, we found that heart‐bound adiponectin was inversely correlated with cardiac hypertrophy, suggesting that heart‐bound adiponectin has a more important function in preventing cardiac hypertrophy than circulating adiponectin. Our study provides new insights regarding the role of adiponectin in diseases.

PS 07-18 HEART-BOUND ADIPONECTIN, NOT SERUM ADIPONECTIN, CORRELATES WITH CARDIAC HYPERTROPHY IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

Objective: The relationship between serum adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. We have previously proposed that tissue-bound adiponectin possibly plays an important role against metabolic syndrome. In this study, we investigated the relationship between heart-bound adiponectin and hypertension or cardiac hypertrophy, compared with serum adiponectin in hypertensive rats. Design and Method: Six-, 12-, and 20-week-old Wistar-Kyoto rats (WKY); 2 subspecies (strains C and B2, characterized by having lower and higher blood pressure, respectively) of spontaneously hypertensive rats (SHR); and stroke-prone SHR (SHRSP) were used. Blood pressure, heart/body ratio, serum adiponectin, and heart-bound adiponectin were measured. Histopathological analyses of the heart were also carried out. Results: The heart/body ratio strongly correlated with blood pressure in 12- and 20-week-old rats, as expected. Serum adiponectin concentration, however, was positively correlated with blood pressure in 12- and 20-week-old rats, and the heart/body ratio and heart muscle cross-sectional area in 20-week-old rats, indicating that there is no relationship between serum adiponectin and blood pressure or cardiac hypertrophy in these rats. In contrast, heart-bound adiponectin in SHRSP was significantly decreased than that in other species of all ages. This results from a decrease in T-cadherin expression, which induces adiponectin binding to tissues. Heart-bound adiponectin inversely correlated with the heart muscle cross-sectional area, but not with blood pressure, indicating that heart-bound adiponectin is more closely related with cardiac hypertrophy than serum adiponectin concentration in these rats. Conclusions: Some researches have reported that serum adiponectin concentration is a useful parameter for evaluating the health condition. Some patients, however, showed hypertension and cardiac hypertrophy despite having high adiponectin concentrations in blood. Our results suggest the possibility that such patients would have decreased heart-bound adiponectin mediated by T-cadherin, and a high adiponectin concentration in blood.

[PS 04-02] EFFECTS OF AN ELASTIN PEPTIDE DERIVED FROM THE BULBUS ARTERIOSUS OF BONITOS ON THE OCCURRENCE OF VASCULAR DAMAGE IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS.

Objective: Elastic fiber, mainly composed by elastin, is an essential structural component of arterial wall and contribute to blood circulation by its elastic property, thus degenerative/destructive changes in elastic fibers cause circulatory disturbance. On the other hand, it has been reported that elastin peptides have diverse biologic roles, including proliferative, chemoattractant and vasorelaxant effects. This study aimed to determine the effects of an elastin peptide derived from the bulbus arteriosus of bonitos on vascular dysfunction in stroke-prone spontaneously hypertensive rats (SHRSPs). Design and Method: Male 15-week-old SHRSP/KPO rats were fed without (control group) or with elastin peptide twice a day at a dose of 600 mg/kg body weight /day for 4 weeks (elastin group). At the end of experiment, histological findings associated with hypertensive nephropathy were observed by light microscopy. Furthermore, using thoracic aortas, we assessed endothelial changes by scanning electron microscopy. Vascular reactivity (contraction and relaxation) and pressure-induced distension were also compared. mRNA levels of endothelial nitric oxide synthase (eNOS) and intercellular adhesion molecule-1 (ICAM-1) were investigated by real-time-polymerase chain reaction. Results: No significant differences were found in blood pressure and vascular reactivity between the control and elastin groups. The incidence of hypertensive arterial changes such as fibrinoid necrosis, or onion-skin-lesion in renal cortex were lower in the elastin group (p < 0.05). Furthermore, the aortas of the elastin group displayed limited endothelial damage compared with those in the control group. ICAM-1 mRNA levels were suppressed in the elastin group, but eNOS levels remained unchanged between groups. Conclusions: In this study, the elastin peptide partially suppressed hypertensive vascular injuries, although it did not delay the occurrence of severe hypertension in SHRSP. Further studies are required to identify the most effective peptide sequence and determine the underlying mechanisms, such as the elastin receptor involved.

Effects of Oxidative Stress on Vascular Reactivity in the Offspring of Protein-Restricted Stroke-Prone Spontaneously Hypertensive Rats

Oxidative stress was induced in 12-week-old offspring of protein-restricted (9% protein) and control (20% protein) protein-restricted stroke-prone spontaneously hypertensive rats (SHRSP) by administering phorbol 12-myristate 13-acetate (PMA) for 4 weeks to determine the effects of oxidative stress on the vascular function of the SHRSP offspring. There was no significant difference in the blood pressure of offspring of the protein-restricted dams and control dams. The plasma diacron-reactive oxygen metabolite (dROM) level at 16 weeks of age was significantly higher in offspring of the protein-restricted dams, whereas the anti-oxidative enzyme activity was similar in both groups. Acetylcholine (Ach)-induced relaxation was significantly reduced in offspring of the protein-restricted dams. The expression of endothelial nitric oxide synthase (eNOS) was lower and the expression of soluble guanylic acid cyclase (sGC) was higher in offspring of the protein-restricted dams. These results indicate that SHRSP offspring of the protein-restricted dams were sensitive to oxidative stress, and displayed the vascular dysfunction.