Biomedical subjects

A Tomohiro

Publications and source records attributed to A Tomohiro.

11 recordsLinked to original sources

PubMed2000

Prevention of doxorubicin (adriamycin)-induced cardiomyopathy by simultaneous administration of angiotensin-converting enzyme inhibitor assessed by acoustic densitometry.

The purpose of our study has to determine the myocardial protective effects of the angiotensin-converting enzyme (ACE) inhibitor temocapril (TEM, 7 mg/kg/day) simultaneously administered with doxorubicin (Adriamycin). Twenty male Sprague-Dawley rats were intraperitoneally administered a cumulative dose of 15 mg/kg of doxorubicin (each dose of 1.0 mg/kg x 15) for 3 weeks, and divided into TEM-untreated and -treated rats. Seven control rats were injected with saline intraperitoneally. Body weight, hemodynamics, and echocardiographic measurements including quantitative analysis of ultrasonic integrated backscatter (IB) were obtained for 12 weeks after treatment. Finally, rats were killed for histopathologic study. At 6 weeks, end-diastolic left ventricular diameter (LVD) and percentage fractional shortening (%FS) were similar in TEM-treated and TEM-untreated rats, but cyclic variation of IB (dB) significantly decreased in TEM-untreated rats (7.3 +/- 1.2; control rats, 9.7 +/- 0.9; p < 0.01). At 12 weeks, %FS decreased in TEM-untreated rats (26.1 +/- 6.1%: TEM-treated rats, 34.2 +/- 6.2; p < 0.05), and calibrated IB (dB) in TEM-untreated rats (15.5 +/- 0.5) increased as compared with that in TEM-treated rats (12.1 +/- 0.7; p < 0.01). Interstitial collagen accumulation increased in TEM-untreated rats and was inhibited in treated rats. Simultaneous administration of TEM with doxorubicin was beneficial in preventing doxorubicin-induced myocardial damage, and myocardial tissue characterization was useful for the early detection of myocardial damage and the assessment of therapy.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2000

Degos' disease with constrictive pericarditis: a case report.

A 47-year-old man with Degos' disease was examined by echocardiography, which showed hypokinesis of the apical left ventricular wall with pericardial effusion. To evaluate the myocardial perfusion and coronary flow reserve, 201Tl scintigraphy and intracoronary Doppler flowmetry were performed. The coronary flow reserve was not decreased nor was there angiographical coronary stenosis, although a pressure study revealed constrictive dysfunction of both ventricles. The constrictive pericarditis might have been induced by pericardial vasculitis, thereby causing the left ventricular wall motion abnormality.

Humans↗

PubMed1997

Regional blood flow in Dahl-Iwai salt-sensitive rats and the effects of dietary L-arginine supplementation.

The purpose of the present study was to determine 1) whether different organs undergo similar increase in vascular resistance in Dahl-Iwai salt-sensitive (S) rats, and 2) the effects of chronic oral L-arginine supplementation on the regional hemodynamics in S rats. Male 6-wk-old S rats and salt-resistant (R) rats were maintained on an 8% NaCl chow for 4 wk. One group (S or R rats) was maintained on tap water and the other group (S/Arg or R/Arg rats) received tap water containing L-arginine at a concentration of 1.5%. Organ blood flow and cardiac output were measured with microspheres in the conscious condition. Mean blood pressure in S, S/Arg, R, and R/Arg rats was 159 +/- 5, 138 +/- 3, 111 +/- 4, and 112 +/- 4 mmHg, respectively. Urinary excretion of protein and albumin in S/Arg rats was significantly suppressed compared with S rats. Concerning regional hemodynamics, the flow rate of the kidney was lower in S rats than in R rats, but there were no differences between S and R rats in the flow rates of the brain, heart, lung, liver, spleen, intestine, skeletal muscle, and skin. Thus the renal blood flow was solely reduced in S rats on a high-salt diet. The flow rate of the kidney in S/Arg rats was maintained at a higher level compared with that of S rats. L-Arginine treatment tended to produce a recovery in the urinary excretion of guanosine 3',5'-cyclic monophosphate in S rats, but had no effect in R rats. Thus the supplementation of L-arginine prevented the increase in blood pressure in S rats on a high-salt diet and normalized the abnormality of renal hemodynamics accompanying salt-induced hypertension.

Animals↗

PubMed1997

Effects of KW-3902, a selective and potent adenosine A1 receptor antagonist, on renal hemodynamics and urine formation in anesthetized dogs.

The purpose of the present investigation was to examine the effects of KW-3902 [8-(noradamantan-3-yl)-1,3-dipropyl-xanthine], a selective and potent adenosine A1 receptor antagonist, in order to clarify the role of adenosine in the control of renal hemodynamics and urine formation in anesthetized dogs. KW-3902 was directly infused into the renal artery to eliminate the systemic effects of the drug. KW-3902 (10 micrograms/kg/min) almost completely inhibited the renal vasoconstriction induced by adenosine via A1 receptors. Intrarenal infusion of KW-3902 did not affect mean arterial pressure, renal blood flow, creatinine clearance, or arterial plasma renin activity, but drastically increased urine flow, urinary excretion of sodium, and osmolar clearance. Inhibition of the renin-angiotensin system using CV-11974 [2-ethoxy-1-((2'-(1-H-tetrazole-5-yl)biphenyl-4-yl) methyl)-1-H-benzimidazole-7-carboxylic acid], a selective AT1 antagonist, did not affect the diuretic action of KW-3902. These data suggest that endogenous adenosine does not play a significant role in the control of renal hemodynamics in whole kidney, but that it plays an important role in preserving body fluid via the A1 receptor independent of the renin-angiotensin system in anesthetized dogs.

Adenosine↗

PubMed1997

The role of basally synthesized nitric oxide in modulating the renal vasoconstrictor action of angiotensin II.

Interactions between nitric oxide (NO) and angiotensin (ANG) II in renal vascular beds were examined in anesthetized dogs. The renal blood flow (RBF) response to an intrarenal arterial injection of ANG II was significantly augmented by intrarenal infusion of the NO synthase inhibitor N(G)-nitro-L-arginine (LNA, 50 microg/kg/min). The simultaneous intrarenal infusion of L-arginine (1 mg/kg/min) prevented the potentiating action of LNA. Similar potentiation was also seen in phenylephrine-induced renal vasoconstriction. Moreover, during simultaneous intrarenal infusion of sodium nitroprusside (SNP), an NO donor, the potentiating action of LNA on the renal vasoconstrictor action of ANG II disappeared. Under these conditions, the released NO stimulated by ANG II was still inhibited by LNA, if present, but basally released NO was resupplied by SNP, as indicated by the return of the RBF. During an infusion of phenylephrine, which produced an increase in renal vascular tone similar to that observed during the infusion of LNA, the renal vasoconstrictor action of ANG II was not augmented. These data suggest that basally released NO plays an important role in the regulation of renal hemodynamics by modulating the renal vasoconstrictor actions of ANG II and phenylephrine.

Angiotensin II↗

PubMed1997

Role of nitric oxide in desmopressin-induced vasodilation of microperfused rabbit afferent arterioles.

We have previously reported that desmopressin (dDAVP) increased the lumen diameter of norepinephrine (NE)-constricted isolated microperfused rabbit afferent arterioles. In this study, we examined the role of nitric oxide in dDAVP-induced vasodilation of afferent arterioles. We microdissected a superficial afferent arteriole from the kidney of a New Zealand white rabbit. Each afferent arteriole was cannulated with a pipette system and microperfused in vitro at 60 mmHg. dDAVP increased the lumen diameter of NE-preconstricted rabbit afferent arterioles dose-dependently. dDAVP-induced vasodilation was abolished by pretreatment with NG-nitro-L-arginine (L-NNA, 10(-4)M) (L-NNA + NE, 6.7 +/- 1.1 microns; L-NNA + NE + dDAVP, 7.3 +/- 1.4 microns, n = 8). dDAVP increased the lumen diameter of NE-preconstricted afferent arterioles pretreated with L-NNA and L-arginine (10(-2)M) (L-NNA + L-arginine + NE, 6.1 +/- 1.1 microns; L-NNA + L-arginine + NE + dDAVP, 8.7 +/- 0.9 microns*; *p < 0.05, n = 6). Aspirin-DL-lysine (10(-4)M) did not influence dDAVP-induced afferent arteriolar vasodilation (aspirin + NE, 6.4 +/- 0.8 microns; aspirin + NE + dDAVP, 9.6 +/- 1.3 microns *; *p < 0.05, n = 5). These results suggest that nitric oxide may be responsible for dDAVP-induced afferent arteriolar vasodilation.

Animals↗

PubMed1997

Dietary L-arginine supplementation normalizes regional blood flow in Dahl-Iwai salt-sensitive rats.

We performed the present study to determine 1) whether different organs undergo similar increase in vascular resistance in Dahl-Iwai salt-sensitive (S) rats, and 2) the effects of chronic oral L-arginine supplementation on the regional hemodynamics in S rats. Male 6 week old S rats and Dahl-Iwai salt-resistant (R) rats were maintained on an 8% NaCl chow for 4 weeks. One group (S or R rats) was maintained on tap water and the other group (S/Arg) of S rats received tap water containing L-arginine at a concentration of 1.5%. Organ blood flow and cardiac output were measured with microspheres in the conscious condition. Concerning regional hemodynamics, the flow rate of the kidney was lower in S rats than in R rats, but there were no differences between S and R rats in the flow rates of the brain, heart, lung, liver, spleen, intestine, skeletal muscle and skin. The flow rate of the kidney in S/Arg rats was maintained at a higher level as compared to that of S rats. Urinary excretion of protein and albumin in S/Arg rats was significantly suppressed when compared to S rats. Thus, the supplementation of L-arginine normalized the abnormality of renal hemodynamics accompanying salt-induced hypertension. It is suggested that the disturbance in the production of nitric oxide may induce salt-sensitive hypertension and the abnormality of renal hemodynamics in the S rats.

Albuminuria↗

PubMed1996

Lack of vasodilatory response in skeletal muscle blood vessels of aged spontaneously hypertensive rats.

Regional hemodynamic responses to the vasodilators, hydralazine (1 mg/kg, i.v.) and verapamil (0.1 mg/kg/min, i.v.), were examined in conscious Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), 15 and 50 weeks of age, using the radioactive microsphere method. The flow rates of heart and skeletal muscle in SHR were higher than those in WKY, and the flow rates of liver, kidney, intestines, and skin in SHR were lower than those in WKY. These differences between the regional blood flow in WKY and SHR were observed in both aged and young rats. The changes in organ blood flow induced by hydralazine and verapamil were similar for WKY and SHR in most organs. Both drugs increased the skeletal muscle blood flow in WKY and young SHR, but not in aged SHR, that is, the skeletal muscle blood vessels in aged SHR lost their vasodilatory response. These results suggest that, although a lack of vasodilatory responses in the skeletal muscle vasculature of aged SHR may be triggered by persistent hypertension, the vital organ vasculature maintains its normal vasodilating capacity.

Age Factors↗

PubMed1996

Vasodilation induced by vasopressin V2 receptor stimulation in afferent arterioles.

We have previously reported that vasopressin (AVP) V2 receptor stimulation increased renal blood flow in dogs anesthetized with pentobarbital. In this study, we examined the direct effects of AVP on afferent arterioles to clarify the role played by V2 receptors in regulating afferent arteriolar tone. We microdissected a superficial afferent arteriole with glomerulus from the kidney of a New Zealand White rabbit. Each afferent arteriole was cannulated with a pipette system and microperfused in vitro at 60 mm Hg. The effects of vasoactive substances were evaluated by changes in the lumen diameter of afferent arterioles. We found that AVP decreased the lumen diameter of microperfused afferent arterioles dose-dependently and that a V1 antagonist, OPC21268, inhibited the vasoconstrictor action of AVP. However, AVP 10(-8) M increased the lumen diameter of norepinephrine (NE)-constricted afferent arterioles pretreated with OPC21268 (OPC + NE, 8.2 +/- 0.7 microns; OPC + NE + AVP, 9.9 +/- 0.9 microns*; *P < 0.05, N = 13). This vasodilatory effect of AVP was abolished by pretreatment with a V2 antagonist, OPC31260. Desmopressin (dDAVP), a V2 agonist, increased the lumen diameter of the NE-constricted afferent arterioles (NE, 7.4 +/- 0.9 microns; NE + dDAVP, 10.1 +/- 0.7 microns*; *P < 0.05, N = 9). These results suggest that AVP V2 receptors are present in rabbit afferent arterioles and that V2 receptor stimulation induces vasodilation in rabbit afferent arterioles.

Animals↗

PubMed1995

Effects of a synthetic rat adrenomedullin on regional hemodynamics in rats.

The effects of rat adrenomedullin, a novel vasorelaxant peptide, on systemic and regional hemodynamics were examined in conscious Sprague Dawley (SD) rats and spontaneously hypertensive rats (SHR). The intravenous infusion of adrenomedullin at rates of 1.67 and 5 micrograms/kg per min decreased the mean arterial pressure in a dose-dependent fashion in both types of rats. Adrenomedullin at a rate of 5 micrograms/kg per min increased the heart rate and cardiac output. As a result, the total peripheral resistance significantly decreased. With regards to the regional hemodynamics, adrenomedullin significantly increased the flow rates in the lungs, heart, spleen, kidneys, adrenal glands and small intestine of SHR. The flow rates in the brain and skin did not change and the flow rates in the skeletal muscle and testis were decreased. These regional hemodynamic changes were also observed in SD rats and there was no qualitative difference in the regional responses to adrenomedullin between SHR and SD rats. Thus, adrenomedullin predominantly increased the flow rates in organs in which adrenomedullin gene was highly expressed. It therefore seems that adrenomedullin may act as a local vasodilatory hormone rather than as a circulatory hormone.

Adrenomedullin↗

PubMed1994

Effects of CV-11974 on renal haemodynamics and renal function in dogs.

The effects of CV-11974, a nonpeptide angiotensin II (Ang II) receptor antagonist, on renal haemodynamics and function were examined in pentobarbital-anaesthetised dogs to evaluate the physiological role of endogenous Ang II in regulating renal haemodynamics and urine formation. Intrarenal infusion of CV-11974 (1 microgram/kg/min) increased renal blood flow (RBF), glomerular filtration rate (GFR), urine flow, and urinary electrolyte excretion (Na and K), with no change in mean arterial pressure (MAP). In another group of dogs, intrarenal infusion of CV-11974 (1 microgram/kg/min) increased the fractional excretion of sodium, the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. CV-11974 did not affect the linear relationship between the free water reabsorption rate (TCH2O) and osmolar clearance (Cosm). These results suggest that endogenous Ang II may play an important role in regulating renal haemodynamics and stimulating sodium reabsorption. Our data indicates that endogenous Ang II may stimulate sodium reabsorption at the proximal and the distal portions of the tubule, with the exception of the medullary portion of the ascending limb of Henle.

Anesthesia↗