The antiadrenergic effect of cyclopentyladenosine on myocardial contractility is reduced in vivo in diabetic rats

1994 ◽  
Vol 72 (10) ◽  
pp. 1245-1251 ◽  
Author(s):  
Fred D. Romano ◽  
Stephen J. Kopp ◽  
June T. Daar ◽  
Cynthia A. Smith
Keyword(s):  
Insulin Treatment ◽  
Left Ventricular Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Adrenergic Agonist ◽  
Experimental Diabetes Mellitus ◽  
Ventricular Performance ◽  
And Control ◽  
Dose Dependent

The aim of this study was to test the hypothesis that the antiadrenergic action of adenosine is reduced in diabetes. This was determined by evaluating the effect of experimental diabetes mellitus on the in vivo myocardial antiadrenergic action of cyclopentyladenosine, an adenosine A1- receptor agonist. Changes in heart rate and ventricular performance in response to infusion of dobutamine, a β1-adrenergic agonist, were determined in the absence and presence of cyclopentyladenosine, in anesthetized, 10- to 12-week male diabetic (60 mg/kg streptozotocin), insulin-treated diabetic and control rats. Intravenous dobutamine (16 μg/kg) increased +dP/dtmax and −dP/dtmax in control rats from 7 706 ± 553 and 5 449 ± 403 mmHg/s (1 mmHg = 133.3 Pa) to 19 170 ± 465 and 8 855 ± 317 mmHg/s, respectively. In diabetic rats dobutamine increased +dP/dtmax and −dP/dtmax from 5 733 ± 541 and 4 016 ± 426 to 15 015 ± 1 521 and 7 039 ± 809 mmHg/s, respectively. Cyclopentyladenosine significantly attenuated dobutamine-stimulated increases in +dP/dtmax and −dP/dtmax in both control and diabetic rats in a dose-dependent (0.1–3.0 μg/kg) manner. Cyclopentyladenosine potency to attenuate dobutamine-enhanced +dP/dtmax was reduced significantly (p < 0.05) in diabetic rats compared with controls (ID50, 1.07 vs. 0.59 μg/kg, respectively) with no change in efficacy. The magnitude of cyclopentyladenosine inhibition of dobutamine-enhanced −dP/dtmax was greater in control than diabetic rats (81 vs. 54%, respectively), but ID50 values were not different. Insulin treatment of diabetic rats prevented the observed changes. These data suggest that the antiadrenergic action of adenosine is compromised in diabetes and that this may contribute to the development of diabetic cardiomyopathy.Key words: adenosine, dobutamine, ventricle, left ventricular pressure, streptozotocin.

Altered sensitivity of chronic diabetic rat heart to calcium

1983 ◽  
Vol 245 (6) ◽  
pp. E560-E567 ◽  
Author(s):  
D. R. Bielefeld ◽  
C. S. Pace ◽  
B. R. Boshell
Keyword(s):  
Rat Heart ◽  
Calcium Metabolism ◽  
Left Ventricular Pressure ◽  
Calcium Sensitivity ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Isolated Hearts ◽  
Pressure Development

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.

Hemodynamic alterations in chronically conscious unrestrained diabetic rats

1987 ◽  
Vol 252 (5) ◽  
pp. H900-H905 ◽  
Author(s):  
L. F. Carbonell ◽  
M. G. Salom ◽  
J. Garcia-Estan ◽  
F. J. Salazar ◽  
M. Ubeda ◽  
...  
Keyword(s):  
Weight Control ◽  
Insulin Treatment ◽  
Cardiac Contractility ◽  
Peripheral Resistance ◽  
Left Ventricular Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic State ◽  
Hemodynamic State ◽  
Male Wistar Rats

Important cardiovascular dysfunctions have been described in streptozotocin (STZ)-diabetic rats. To determine the influence of these changes on the hemodynamic state and whether insulin treatment can avoid them, different hemodynamic parameters, obtained by the thermodilution method, were studied in STZ-induced (65 mg/kg) diabetic male Wistar rats, as well as in age-control, weight-control, and insulin-treated diabetic ones. All rats were examined in the conscious, unrestrained state 12 wk after induction of diabetes or acidified saline (pH 4.5) injection. At 12 wk of diabetic state most important findings were normotension, high blood volume, bradycardia, increase in stroke volume, cardiac output, and cardiosomatic ratio, and decrease in total peripheral resistance and cardiac contractility and relaxation (dP/dtmax and dP/dtmin of left ventricular pressure curves). The insulin-treated diabetic rats did not show any hemodynamic differences when compared with the control animals. These results suggest that important hemodynamic alterations are present in the chronic diabetic state, possibly conditioning congestive heart failure. These alterations can be prevented by insulin treatment.

Mechanical interaction between the ventricles during systole

1977 ◽  
Vol 55 (3) ◽  
pp. 373-382 ◽  
Author(s):  
B. Lowell Langille ◽  
David R. Jones
Keyword(s):  
Left Ventricle ◽  
Right Ventricular ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Mechanical Interaction ◽  
Rigor Mortis ◽  
Ventricular Performance ◽  
Ventricular Afterload

The immediate effect of abrupt alteration in the function of either ventricle on pressures in both ventricles has been examined in rabbits. Increasing left ventricular afterload, by aortic occlusion, caused a marked increase in peak left ventricular pressure (an increase of 44.0 ± 5.7 mmHg, from a mean of 79.4 ± 3.4 mmHg) and simultaneously a significant increase (an increase of 3.8 ± 0.6 mmHg, from a mean of 24.2 ± 1.4 mmHg) in right ventricular pressure. On the other hand, when similar increases in left ventricular pressure were induced by sudden changes in preload no alteration in right ventricular pressure was seen. High-frequency oscillatory infusion of saline into the left ventricle produced coincident oscillations in both ventricular pressures during systole. Left ventricular pressure generation was affected by interventions with right ventricular performance which altered afterload or preload and, although interaction was minimal at normal physiological pressures, a significant interaction was observed during induced systemic hypotension. A direct transference of pressure from right to left ventricle, comparable with that seen in vivo, was also observed when the ventricles of excised hearts in rigor mortis were inflated with saline. It is concluded that mechanical interaction occurs between the ventricles during systole and, consequently, the ventricles cannot be treated as mechanically independent pumps.

In vivo safety and accuracy of a clinically applicable telemetered left ventricular pressure module: intermediate-term results

2004 ◽  
Vol 10 (4) ◽  
pp. S67 ◽  
Author(s):  
Patrick I. McConnell ◽  
Daise de Cunha ◽  
Tanya Shipkowitz ◽  
Justin Van Hee ◽  
Phillip H. Long ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Ventricular Pressure

scholarly journals Possible mechanism of the cardio-renal protective effects of AVE-0991, a non-peptide Mas-receptor agonist, in diabetic rats

2012 ◽  
Vol 13 (3) ◽  
pp. 334-340 ◽  
Author(s):  
Kulwinder Singh ◽  
Kuldeepak Sharma ◽  
Manjeet Singh ◽  
PL Sharma
Keyword(s):  
Blood Pressure ◽  
Receptor Agonist ◽  
Diastolic Pressure ◽  
Left Ventricular Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Ventricular Pressure ◽  
Protective Effects ◽  
Mas Receptor ◽  
Arterial Blood

Hypothesis: This study was designed to investigate the cardio-renal protective effect of AVE-0991, a non-peptide Mas-receptor agonist, and A-779, a Mas-receptor antagonist, in diabetic rats. Materials and methods: Wistar rats treated with streptozotocin (50 mg/kg, i.p., once), developed diabetes mellitus after 1 week. After 8 weeks, myocardial functions were assessed by measuring left ventricular developed pressure (LVDP), rate of left ventricular pressure development (d p/d tmax), rate of left ventricular pressure decay (d p/d tmin) and left ventricular end diastolic pressure (LVEDP) on an isolated Langendorff’s heart preparation. Further, mean arterial blood pressure (MABP) was measured by using the tail-cuff method. Assessment of renal functions and lipid profile was carried out using a spectrophotometer. Results: The administration of streptozotocin to rats produced persistent hyperglycaemia, dyslipidaemia and hypertension which consequently produced cardiac and renal dysfunction in 8 weeks. AVE0991 treatment produced cardio-renal protective effects, as evidenced by a significant increase in LVDP, d p/d tmax, d p/d tmin and a significant decrease in LVEDP, BUN, and protein urea. Further, AVE-0991 treatment for the first time has been shown to reduce dyslipidaemia and produced antihyperglycaemic activity in streptozotocin-treated rats. However, MABP and creatinine clearance remained unaffected with AVE-0991 treatment. Conclusions: AVE-0991 produced cardio-renal protection possibly by improving glucose and lipid metabolism in diabetic rats, independent of its blood pressure lowering action.

Myocardial substrate metabolism influences left ventricular energetics in vivo

2000 ◽  
Vol 278 (4) ◽  
pp. H1345-H1351 ◽  
Author(s):  
Christian Korvald ◽  
Odd Petter Elvenes ◽  
Truls Myrmel
Keyword(s):  
Fatty Acid ◽  
Coronary Flow ◽  
Left Ventricular Pressure ◽  
Random Order ◽  
Left Ventricular ◽  
Acid Oxidation ◽  
Left Ventricular Volumes ◽  
Acid Consumption ◽  
Myocardial Substrate

The myocardial oxygen consumption (MV˙o 2) to left ventricular pressure-volume area (PVA) relationship is assumed unaltered by substrates, despite varying phosphate-to-oxygen ratios and possible excess MV˙o 2 associated with fatty acid consumption. The validity of this assumption was tested in vivo. Left ventricular volumes and pressures were assessed with a combined conductance-pressure catheter in eight anesthetized pigs. MV˙o 2 was calculated from coronary flow and arterial-coronary sinus O2 differences. Metabolism was altered by glucose-insulin-potassium (GIK) or Intralipid-heparin (IH) infusions in random order and monitored with [14C]glucose and [3H]oleate tracers. Profound shifts in glucose and fatty acid oxidation were observed. Contractility, coronary flow, and slope of the MV˙o 2-PVA relationship were unchanged during GIK and IH infusions. MV˙o 2 at zero PVA (unloaded MV˙o 2) was 0.16 ± 0.13 J ⋅ beat− 1 ⋅ 100 g− 1 higher during IH compared with GIK infusion ( P = 0.001), a 48% increase. The study demonstrates a marked energetic advantage of glucose oxidation in the myocardium, profoundly affecting the MV˙o 2-PVA relationship. This may in part explain the “oxygen-wasting” effect of lipid-enhancing interventions such as adrenergic drugs and ischemia.

Heat stress protects aged hypertrophied and nonhypertrophied rat hearts against ischemic damage

1997 ◽  
Vol 273 (3) ◽  
pp. H1333-H1341 ◽  
Author(s):  
R. N. Cornelussen ◽  
A. V. Garnier ◽  
M. M. Vork ◽  
P. Geurten ◽  
R. S. Reneman ◽  
...  
Keyword(s):  
Heat Stress ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Treatment ◽  
Sham Operation ◽  
Hsp 70 ◽  
Rat Hearts ◽  
Developed Pressure ◽  
And Control ◽  
Postischemic Recovery

To explore the effects of heat stress (HS) in aged hypertrophied and nonhypertrophied rat hearts, postischemic recovery was investigated 15 mo after aortic constriction (AoB) or sham operation (Sham). Twenty-four hours after HS (42 degrees C; 15 min) or control treatment (normothermia), global ischemia was induced for 20 min in isolated AoB hearts and for 20 or 30 min in Sham hearts. After HS, postischemic recovery after 20-min ischemia in AoB hearts and 30-min ischemia in Sham hearts, respectively, was significantly better than in corresponding controls. In AoB hearts, cardiac output (CO), left ventricular developed pressure (LVDP), and the positive maximal first derivative of left ventricular pressure (+dP/dtmax) recovered to 33 +/- 26 (means +/- SD), 87 +/- 5, and 72 +/- 12%, respectively, after HS and to 5 +/- 8, 22 +/- 39, and 17 +/- 29% of preischemic values, respectively, in controls. Postischemic arrhythmias were significantly reduced in HS hypertrophied hearts, but creatine kinase (CK) loss was not reduced. In Sham hearts subjected to 30 min ischemia, CO, LVDP, and +dP/dtmax recovered to 20 +/- 20, 75 +/- 8, and 59 +/- 15%, respectively, after HS and to 3 +/- 8, 21 +/- 32, and 16 +/- 32% of preischemic values, respectively, in controls. Duration of arrhythmias and CK loss were not reduced in the heated hearts. When Sham hearts were subjected to only 20-min ischemia, functional recovery was not different in HS and control hearts, indicating that HS pretreatment extends the ischemic interval before irreversible injury occurs in the heart. In all HS Sham hearts, the myocardial 72-kDa HS protein (HSP 70) content was significantly increased. However, in HS AoB hearts, HSP 70 levels were not significantly different from the values in the control hearts. These results indicate that HS pretreatment induces cardioprotection in aged hypertrophied and nonhypertrophied rat hearts, which, however, cannot be unequivocally related to increased HSP 70 tissue contents.

Time course of changes in albumin synthesis and mRNA in diabetic and insulin-treated diabetic rats

1985 ◽  
Vol 248 (6) ◽  
pp. E656-E663 ◽  
Author(s):  
D. E. Peavy ◽  
J. M. Taylor ◽  
L. S. Jefferson
Keyword(s):  
Total Protein ◽  
Time Course ◽  
Insulin Treatment ◽  
Relative Rate ◽  
Cdna Probe ◽  
Diabetic Rats ◽  
Rate Of Change ◽  
Albumin Synthesis ◽  
Albumin Mrna

Albumin synthesis in rat liver in vivo decreased from 12.7 to 2.2% of total protein synthesis during the first 3 days after the induction of diabetes and then remained relatively constant at this depressed rate for another 3 days. Insulin treatment begun on the 3rd day after the induction of diabetes restored albumin synthesis to control values within 3 days. Hybridization of total polyadenylate-containing RNA with a specific albumin cDNA probe revealed a close correspondence between the relative abundance of albumin mRNA and the relative rate of albumin synthesis after induction of diabetes and in response to insulin treatment. The apparent half-life of albumin mRNA, based on the rate of change of the message from one steady-state level to another, was approximately 22 h in both diabetic and insulin-treated diabetic rats. Diabetes of 3-day duration had no effect on the average sizes of total and albumin-synthesizing polysomes or on the ribosomal half-transit time for total protein and albumin. However, the number of albumin-synthesizing polysomes decreased as a result of diabetes to approximately one-third the number found in control livers. Taken together the results indicate that albumin synthesis was regulated by the availability of albumin mRNA and not by alterations in degradation, sequestration, or translation of message.

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