Biomedical subjects

Ryo Oikawa

Publications and source records attributed to Ryo Oikawa.

9 recordsLinked to original sources

PubMed2006

Vasopressin V1A receptor enhances baroreflex via the central component of the reflex arc.

The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts its physiological actions via 3 distinct receptor isoforms designated V1A, V1B, and V2. We recently showed that V1A receptor was involved in the baroreflex control of heart rate using V1A receptor knockout mice. The present study was undertaken to further clarify this finding. In conscious mice, resting blood pressure of the knockout group was lower than that of the wild-type group (wild-type, 108+/-2.0 mm Hg; knockout, 98+/-3.8 mm Hg; n=6-7) without notable change in heart rate. Although phenylephrine and nitroprusside-induced changes in blood pressure did not differ in these strains, the subsequent bradycardia and tachycardia were markedly blunted in the knockout mice (mean slopes for baroreflex curve after phenylephrine treatment; wild-type, -5.65+/-0.30 bpm/mm Hg; knockout, -3.97+/-0.52 bpm/mm Hg; those after nitroprusside treatment; wild-type, -0.51+/-0.10 bpm/mm Hg; knockout, -0.18+/-0.05 bpm/mm Hg; n=6-7). Under urethane anesthesia (1.0-1.2 g/kg, i.p.), electrical stimulation of the vagal afferent nerve evoked frequency-dependent hypotension and bradycardia in the wild-type mice. In contrast, in the knockout mice such stimulation induced a pressor, not a depressor, response and diminished bradycardia. Moreover, electrical stimulation-induced hemodynamic changes through the vagal afferent nerve in the wild-type mice were significantly attenuated by pretreatment with intravenously administered V1A receptor antagonist d(CH(2))(5)Tyr(Me)AVP. Electrical stimulation of the vagal efferent nerve-induced hemodynamic changes (depressor and bradycardia) and chronotropic responses to adrenergic and cholinergic stimuli were not different between the 2 strains. These results suggest that the V1A receptor in the central nervous system is involved in the regulation of the heart rate via the baroreflex arc.

Animals↗

PubMed2006

V1a vasopressin receptors maintain normal blood pressure by regulating circulating blood volume and baroreflex sensitivity.

Arginine-vasopressin (AVP) is a hormone that is essential for both osmotic and cardiovascular homeostasis, and exerts important physiological regulation through three distinct receptors, V1a, V1b, and V2. Although AVP is used clinically as a potent vasoconstrictor (V1a receptor-mediated) in patients with circulatory shock, the physiological role of vasopressin V1a receptors in blood pressure (BP) homeostasis is ill-defined. In this study, we investigated the functional roles of the V1a receptor in cardiovascular homeostasis using gene targeting. The basal BP of conscious mutant mice lacking the V1a receptor gene (V1a-/-) was significantly (P < 0.001) lower compared to the wild-type mice (V1a+/+) without a notable change in heart rate. There was no significant alteration in cardiac functions as assessed by echocardiogram in the mutant mice. AVP-induced vasopressor responses were abolished in the mutant mice; rather, AVP caused a decrease in BP, which occurred in part through V2 receptor-mediated release of nitric oxide from the vascular endothelium. Arterial baroreceptor reflexes were markedly impaired in mutant mice, consistent with a loss of V1a receptors in the central area of baroreflex control. Notably, mutant mice showed a significant 9% reduction in circulating blood volume. Furthermore, mutant mice had normal plasma AVP levels and a normal AVP secretory response, but had significantly lower adrenocortical responsiveness to adrenocorticotropic hormone. Taken together, these results indicate that the V1a receptor plays an important role in normal resting arterial BP regulation mainly by its regulation of circulating blood volume and baroreflex sensitivity.

Adrenal Cortex↗

PubMed2006

Possible involvement of calpain activation in pathogenesis of chronic heart failure after acute myocardial infarction.

Changes in proteolytic activity of the myocardium during the development of heart failure after left coronary artery ligation (CAL) of rats were examined. Hemodynamics of the rats at the eighth week (8w-CAL rat), but not at the second week (2w-CAL rat), after CAL showed the symptoms of chronic heart failure. Contents of mu-calpin and m-calpain, but not an intrinsic calpain inhibitor calpastatin, in the viable left ventricular muscle (viable LV) and the right ventricular muscle (RV) of the 2w-CAL and 8w-CAL rats were increased, which was associated with an elevation of intrinsic activities of leupeptin-sensitive, Ca(2+)-activated proteolysis in the cytosolic fractions of the viable LV and RV. Oral administration of 3 mg/kg/d trandolapril or 1 mg/kg/d candesartan from the second to eighth week after CAL improved the hemodynamics of 8w-CAL rats. The drug treatment attenuated the increases in mu-calpain and m-calpain contents and the elevation of the proteolytic activity of the viable LV and RV in the 8w-CAL rat. The drug treatment increased calpastatin content of the RV in the 8w-CAL rat. These results suggest that sustained activation of calpain is involved in the development of chronic heart failure and that trandolapril and candesartan prevent the activation of calpains after CAL.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Effects of angiotensin I-converting enzyme inhibitor and angiotensin II type 1 receptor blocker on the right ventricular sarcoglycans and dystrophin after left coronary artery ligation.

We examined the effects of trandolapril and candesartan on changes in the levels of sarcoglycans and dystrophin in the right ventricle of rats with the left coronary artery ligation. Hemodynamic and morphological alterations suggested the development of hypertrophy of the right ventricle and chronic heart failure by the 8th week. By the end of the 8th week, alpha- and beta-sarcoglycans and dystrophin were decreased. Increases in mu- and m-calpains in the hypertrophied right ventricle were associated with an elevation of casein-proteolytic activity in the cytosolic fraction. Oral administration of 3 mg/kg/day trandolapril or 1 mg/kg/day candesartan from the 2nd to 8th week after the left coronary artery ligation attenuated decreases in alpha-sarcoglycan and dystrophin and reduced the increased proteolytic activity. The results suggest that attenuation of decreases in sarcoglycans and dystrophin is a possible mechanism underlying trandolapril- and candesartan-mediated improvement of structural and functional alterations of the right ventricle in the coronary artery-ligated rat.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2005

Effects of ACE inhibitor and AT1 blocker on dystrophin-related proteins and calpain in failing heart.

OBJECTIVES: Genetic depletion of dystrophin-related protein (DRP) complex causes cardiomyopathy in animals and humans. We found in a previous study that some types of DRP were degraded and that calpain content was increased in rats with non-genetically induced heart failure. The present study was aimed at examining the effects of an angiotensin-I-converting enzyme inhibitor (ACEI) trandolapril (Tra) or an angiotensin II type 1 receptor blocker (ARB) candesartan (Can), both of which are known to improve the pathophysiology of chronic heart failure (CHF) on degradation of DRP in failing hearts. METHODS: Coronary artery-ligated (CAL) and sham-operated rats (Sham rats) were treated orally with 3 mg/kg/day trandolapril (Tra) or 1 mg/kg/day candesartan (Can) from the 2nd to 8th week after surgery. RESULTS: Hemodynamic parameters of CAL rats at the 8th week after CAL (8w-CAL) indicated heart failure. alpha-Sarcoglycan (SG) and dystrophin in the surviving left ventricle (surviving LV) of 8w-CAL rats decreased, whereas beta-, gamma-, and delta-SGs remained unchanged. Calcium-activated neutral proteases mu-calpain and m-calpain increased in the surviving LV at the 8th week of postmyocardial infarction. Proteolytic activity in the presence of 5 mM Ca2+ markedly increased at the 2nd and 8th weeks, whereas 50 microM Ca2+ slightly but significantly increased proteolysis of casein. Tra or Can treatment improved the hemodynamic parameters, attenuated changes in alpha-SG and dystrophin, and reversed both calpain contents and activities of the failing heart back to sham levels. CONCLUSION: These results suggest that attenuation in calpain-induced degradation of DRP complex is a possible mechanism for the Tra- or Can-mediated improvement of the pathogenesis of CHF following myocardial infarction.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2005

Preferable anesthetic conditions for echocardiographic determination of murine cardiac function.

Ketamine and xylazine are routinely used for measurement of hemodynamics of mice and rats by echocardiography. The anesthetic agents produce low heart rate (HR) in the animals, which may result in misleading data in the hemodynamic profiles of the small animals. The purpose of the present study was to select an appropriate anesthetic condition in the evaluation of mouse and rat cardiac function by echocardiography. Echocardiographic measurement was performed in male C57BL6 mice anesthetized with an intraperitoneal injection of 30 or 40 mg/kg pentobarbital (P30 or P40) or a combination of 60 mg/kg ketamine and 6 mg/kg xylazine (KX) and in male Wistar rats with an intraperitoneal injection of 40 or 50 mg/kg pentobarbital (P40 or P50) or a combination of 100 mg/kg ketamine and 10 mg/kg xylazine (KX). Basal HR of P30-anesthetized mice and P40-anesthetized were comparable to those in the conscious state, whereas KX-anesthetized mice and rats were 38% and 74% of those of the conscious animals, respectively. Fractional shortening (FS) and cardiac output index (COI) of the P30-anesthetized mice or the P40-anesthetized rats were greater than those of KX-anesthetized animals. Intraperitoneal injection of dobutamine at 0.3 and 1 mg/kg increased HR, FS, and COI of the P30-anesthetized mice and the P40-anesthetized rats, respectively, whereas the percent responses of these parameters in KX animals were greater than those in pentobarbital-anesthetized ones due to the lower basal values for the cardiac functional parameters. Anesthesia with P30 for the mouse and P40 for the rat rather than ketamine/xylazine may be relevant to the evaluation of cardiac function using echocardiography.

Adrenergic beta-Agonists↗

PubMed2004

Two alpha1-adrenergic receptor subtypes regulating the vasopressor response have differential roles in blood pressure regulation.

To study the functional role of individual alpha1-adrenergic (AR) subtypes in blood pressure (BP) regulation, we used mice lacking the alpha1B-AR and/or alpha1D-AR with the same genetic background and further studied their hemodynamic and vasoconstrictive responses. Both the alpha1D-AR knockout and alpha1B-/alpha1D-AR double knockout mice, but not the alpha1B-AR knockout mice, had significantly (p < 0.05) lower levels of basal systolic and mean arterial BP than wild-type mice in nonanesthetized condition, and they showed no significant change in heart rate or in cardiac function, as assessed by echocardiogram. All mutants showed a significantly (p < 0.05) reduced catecholamine-induced pressor and vasoconstriction responses. It is noteworthy that the infusion of norepinephrine did not elicit any pressor response at all in alpha1B-/alpha1D-AR double knockout mice. In an attempt to further examine alpha1-AR subtype, which is involved in the genesis or maintenance of hypertension, BP after salt loading was monitored by tail-cuff readings and confirmed at the endpoint by direct intra-arterial recording. After salt loading, alpha1B-AR knockout mice developed a comparable level of hypertension to wild-type mice, whereas mice lacking alpha1D-AR had significantly (p < 0.05) attenuated BP and lower levels of circulating catecholamines. Our data indicated that alpha1B- and alpha1D-AR subtypes participate cooperatively in BP regulation; however, the deletion of the functional alpha1D-AR, not alpha1B-AR, leads to an antihypertensive effect. The study shows differential contributions of alpha1B- and alpha1D-ARs in BP regulation.

Animals↗

PubMed2004

Induction of heat shock protein 72 in the failing heart is attenuated after an exposure to heat shock.

Induction of heat shock protein (Hsp) 72 in the right ventricular muscle of the rat with heart failure following acute myocardial infarction (AMI) was examined. AMI was induced by the left coronary artery ligation (CAL). The animals at the 8th, but not 2nd, week after CAL revealed a decrease in cardiac output index (COI), suggesting that heart failure had developed by 8 weeks after CAL. Increases in the right ventricular developed pressure and the ratios of right ventricle/body weight and lung/body weight at the 2nd and 8th weeks showed the development of the right ventricular hypertrophy. After measurement of hemodynamic parameters, the hearts isolated from animals at the 2nd and 8th weeks after CAL (2w- and 8w-CAL hearts, respectively) were perfused and subjected to heat shock (at 42 degrees C, for 15 min) followed by 6-h perfusion. At the end of perfusion, Hsp72 content in the left ventricle without infarct area (viable LV) and the right ventricle (RV) was determined by the Western immunoblotting method. The production of myocardial Hsp72 in the viable LV and RV of the 2w-CAL heart increased after an exposure to heat shock. In contrast, induction of Hsp72 in the viable LV and RV of the 8w-CAL heart was blunted. The results suggest that the development of heart failure following AMI may result in a decrease in the ability for Hsp72 induction not only in the viable LV but also in the RV, leading to contractile dysfunction of the heart.

Animals↗

PubMed2003

Decrease in sarcoglycans and dystrophin in failing heart following acute myocardial infarction.

OBJECTIVE: Genetic defects in several sarcoglycans (SGs) and dystrophin (Dys) play a critical role in cardiomyopathy. The present study was designed to determine whether changes in SGs and Dys might occur in animals with chronic heart failure (CHF) induced by acute myocardial infarction (AMI), which have no genetic defects. METHODS: AMI was induced by the left coronary artery ligation (CAL) in rats. The hemodynamic parameters of the 2- and 8-week CAL (2w- and 8w-CAL) rats were measured and the myocardial SGs, Dys, calpain, and calpastatin levels were determined by the Western blot method. Myocardial calpain-like protease activity was evaluated as caseinolysis activity. RESULTS: Increases in left ventricular end-diastolic pressure (LVEDP) and right ventricular systolic pressure, and a decrease in +/-dP/dt were observed at the 2nd week, whereas cardiac output index (COI) was preserved. In contrast, the 8w-CAL rats showed a further increment in LVEDP with low COI. alpha-SG of the viable left ventricle (LV), and septum (Sep) of the 8w-CAL rat decreased (60-70% of the control). The alpha- and beta-SGs of the right ventricle (RV) of the 2w- and 8w-CAL rats were reduced, while gamma- and delta-SGs in the three regions did not change significantly. Dys in the viable LV and RV of the 8w-CAL rat decreased (75% of the control). The amount of m-calpain in the three regions of the 2w- and 8w-CAL rats increased (140-200% of the control), whereas the endogenous calpain inhibitor, calpastatin, did not change significantly. The in vitro degradation studies using purified m-calpain or cytosolic fractions of the 8w-CAL rat heart suggested a reduction in SGs and Dys by calpain. CONCLUSION: The results suggest that a decrease in SGs and Dys may play an important role in the pathophysiology of CHF following AMI.

Animals↗