Chronotropic function in spontaneously diabetic BB rats

1989 ◽  
Vol 67 (5) ◽  
pp. 519-521 ◽  
Author(s):  
Sasanka Ramanadham ◽  
Gail M. McGrath ◽  
John H. McNeill
Keyword(s):  
Direct Consequence ◽  
Wistar Rat ◽  
Diabetic Rats ◽  
Chronotropic Effect ◽  
Chronotropic Response ◽  
Bb Rats ◽  
Streptozotocin Diabetic Rats ◽  
Chronotropic Effects ◽  
Altered Thyroid ◽  
Positive Chronotropic Effect

In the present study, isolated atrial function in spontaneously diabetic BB Wistar rats maintained for 12 weeks on a low (BB-LI) and a high (BB-HI) dosage of insulin was examined. Basal atrial rates were unchanged in the diabetic animals, relative to nondiabetic littermates (ND-BB) or Wistar controls. The BB-HI animals were euglycemic and responded to isoproterenol in a similar manner to the ND-BB and Wistar control animals. In contrast, BB-LI animals remained hyperglycemic and exhibited lower responses to the maximum chronotropic effects of isoproterenol. Plasma thyroid hormone levels were unaltered in the BB-diabetic animals. These results therefore reveal an absence of bradycardia and hypothyroidism in spontaneously diabetic BB rats, in contrast to previous observations in streptozotocin diabetic rats. However, a decrease in chronotropic response to isoproterenol was still noted in the BB-LI animals. These findings suggest that decreased positive chronotropic effect of isoproterenol in diabetes may not be a direct consequence of altered thyroid status.Key words: BB Wistar rat, diabetes, chronotropic response, β-receptors.

Effects of chronic streptozotocin-induced diabetes on the cardiac responses to milrinone

1985 ◽  
Vol 63 (12) ◽  
pp. 1620-1623 ◽  
Author(s):  
Ramesh K. Goyal ◽  
John H. McNeill
Keyword(s):  
Left Atrium ◽  
Right Atrium ◽  
Diabetic Rats ◽  
Chronotropic Response ◽  
Cardiac Responses ◽  
Streptozotocin Induced Diabetes ◽  
Streptozotocin Diabetic Rats ◽  
Dose Dependent ◽  
Right Atria ◽  
Positive Chronotropic Effect

We have studied the effects of milrinone on various cardiac preparations obtained from 6-week streptozotocin diabetic rats. The basal rate of spontaneously beating right atrium from diabetics was significantly lower as compared with controls. Milrinone (5 × 10−5 to 8 × 10−4 M) produced a dose-dependent positive inotropic and positive chronotropic effect in left atrium and right atrium, respectively. The positive chronotropic response to milrinone was slightly increased in right atria from diabetic animals. In papillary muscle neither the maximum response nor the pD2 value of milrinone was altered significantly in diabetic animals. The pD2 values of milrinone in right atrium and left atrium were found to be significantly higher in diabetic preparations compared with controls. The data indicate that the responses to milrinone are either unchanged or enhanced in hearts from diabetic animals.

scholarly journals Metabolic and functional consequences of cytosolic 5′-nucleotidase-IA overexpression in neonatal rat cardiomyocytes

2003 ◽  
Vol 285 (3) ◽  
pp. H991-H998 ◽  
Author(s):  
Graciela B. Sala-Newby ◽  
Nicola V. E. Freeman ◽  
Maria A. Curto ◽  
Andrew C. Newby
Keyword(s):  
Neonatal Rat ◽  
Nucleoside Transporter ◽  
Chronotropic Effect ◽  
Rat Cardiomyocytes ◽  
Adenosine Receptor Antagonist ◽  
Neonatal Rat Cardiomyocytes ◽  
Functional Consequences ◽  
Chronotropic Effects ◽  
Simulated Hypoxia ◽  
Positive Chronotropic Effect

Adenosine exerts a spectrum of energy-preserving actions on the heart negative chronotropic effects. The pathways leading to adenosine formation have remained controversial. In particular, although cytosolic 5′-nucleotidases can catalyze adenosine formation in cardiomyocytes, their contribution to the actions of adenosine has not been documented previously. We recently cloned two closely related AMP-preferring cytosolic 5′-nucleotidases (cN-IA and -IB); the A form predominates in the heart. In this study, we overexpressed pigeon cN-IA in neonatal rat cardiomyocytes using an adenovirus. cN-IA overexpression increased adenosine formation and release into the medium caused by simulated hypoxia and by isoproterenol in the absence and presence of inhibitors of adenosine metabolism. Adenosine release was not affected by an ecto-5′-nucleotidase inhibitor, α,β-methylene-ADP, but was affected by a nucleoside transporter, dipyridamole. The positive chronotropic effect of isoproterenol (130 ±3 vs. 100 ±4 beats/min) was inhibited (107 ±3 vs. 94 ±3 beats/min) in cells overexpressing cN-IA, and this was reversed by the addition of the adenosine receptor antagonist 8-( p-sulfophenyl)theophilline (120 ± 3 vs. 90 ± 4 beats/min). Our results demonstrate that overexpressed cN-IA can be sufficiently active in cardiomyocytes to generate physiologically effective concentrations of adenosine at its receptors.

Bradykinin induced a positive chronotropic effect via stimulation of T- and L-type calcium currents in heart cells

2003 ◽  
Vol 81 (3) ◽  
pp. 247-258 ◽  
Author(s):  
Nesrine El-Bizri ◽  
Ghassan Bkaily ◽  
Shimin Wang ◽  
Danielle Jacques ◽  
Domenico Regoli ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Ionic Current ◽  
Calcium Currents ◽  
Heart Cells ◽  
Dependent Manner ◽  
Chronotropic Effect ◽  
Chick Heart ◽  
Chronotropic Effects ◽  
Positive Chronotropic Effect ◽  
Stimulation Of

Using Fluo-3 calcium dye confocal microscopy and spontaneously contracting embryonic chick heart cells, bradykinin (10–10 M) was found to induce positive chronotropic effects by increasing the frequency of the transient increase of cytosolic and nuclear free Ca2+. Pretreatment of the cells with either B1 or B2 receptor antagonists (R126 and R817, respectively) completely prevented bradykinin (BK) induced positive chronotropic effects on spontaneously contracting single heart cells. Using the whole-cell voltage clamp technique and ionic substitution to separate the different ionic current species, our results showed that BK (10–6 M) had no effect on fast Na+ inward current and delayed outward potassium current. However, both L- and T-type Ca2+ currents were found to be increased by BK in a dose-dependent manner (10–10–10–7 M). The effects of BK on T- and L-type Ca2+ currents were partially blocked by the B1 receptor antagonist [Leu8]des-Arg9-BK (R592) (10–7 M) and completely reversed by the B2 receptor antagonist D-Arg[Hyp3,D-Phe7,Leu8]BK (R-588) (10–7 M) or pretreatment with pertussis toxin (PTX). These results demonstrate that BK induced a positive chronotropic effect via stimulation of T- and L-type Ca2+ currents in heart cells mainly via stimulation of B2 receptor coupled to PTX-sensitive G-proteins. The increase of both types of Ca2+ current by BK in heart cells may explain the positive inotropic and chronotropic effects of this hormone.Key words: chick heart cells, bradykinin, B1 receptor, B2 receptor, Ca2+, Na+, K+ currents.

Intrathyroidal thyroglobulin in streptozotocin-diabetic rats

1986 ◽  
Vol 112 (4) ◽  
pp. 552-558 ◽  
Author(s):  
Luis Lamas ◽  
Trinidad Jolin
Keyword(s):  
Sedimentation Coefficient ◽  
Iodine Content ◽  
Direct Consequence ◽  
Diabetic Rats ◽  
Streptozotocin Diabetic Rats ◽  
The Stability ◽  
Low Ionic Strength ◽  
Internal Marker ◽  
Two Peaks ◽  
Intermediate Situation

Abstract. In order to elucidate whether or not the 'coupling defect' observed in thyroids from diabetic rats is due to a structural defect of intrathyroidal thyroglobulin (Tg), the sedimentation pattern and the stability of the thyroidal soluble iodoproteins were studied in control (C), food restricted (FR), diabetic (D) and insulin-treated diabetic (D+I) rats fed a low iodine diet either with (NID) or without (LID) iodide supplementation and labelled with 125I: 1) acutely, 24 h prior to sacrifice and 2) chronically, by feeding the corresponding diet labelled for 60 days. Diabetes resulted in a decrease of thyroidal weight, an increase of both thyroidal 127I content and concentration and decreased plasma TSH, irrespective of the diet. Insulin treatment reversed these alterations. Food restriction led to an intermediate situation between C and D. The iodoamino acid distribution in the acutely labelled thyriodal soluble iodoproteins showed a significant increase in the percent of organified 125I found as iodotyrosines (MIT and DIT) and a decrease of that found as iodothyronines (T3 and T4) both in D and FR. However, in the isotopically equilibrated groups, no differences were found except in LID-D where a slight increase in DIT and a decrease in T3 was found as compared to the corresponding control. The sedimentation patterns of both acutely and chronically labelled thyroidal soluble iodoproteins from all experimental groups displayed two peaks. The main one, corresponding to Tg, had a slightly lower sedimentation coefficient than the 19 S internal marker run in parallel, while the second one, relatively small, formed probably by dissociation of the main Tg peak, sedimented more slowly (12–14 S). D and FR showed no differences with C and D+I, however, the Tg molecule from D and FR was more resistant to the dissociating effect of dialysis against low ionic strength buffer than the corresponding C and D+I groups. This increase in stability of Tg in D and FR might be due to their relatively higher iodine content and/or lower TSH stimulation. In conclusion, the results obtained suggest that the low T3 and T4 content of thyroidal soluble iodoproteins found in diabetic rats is not the direct consequence of a major structural alteration in the Tg molecule.

Sustained increases in heart rate induced by timed repetition of vagal stimulation in dogs

1985 ◽  
Vol 249 (4) ◽  
pp. H703-H709
Author(s):  
T. Yang ◽  
M. D. Jacobstein ◽  
M. N. Levy
Keyword(s):  
Cycle Length ◽  
Cardiac Cycle ◽  
Vagal Stimulation ◽  
Sinus Node ◽  
Critical Time ◽  
Critical Value ◽  
Chronotropic Effect ◽  
Chronotropic Response ◽  
The Right ◽  
Positive Chronotropic Effect

We determined the influence of the "free-running cycle length" (tau FR) on chronotropic responses to one burst of right vagal stimuli per cardiac cycle in anesthetized dogs (tau FR, cycle length that prevailed in absence of right vagal stimulation). We varied tau FR by the following methods: 1) tonic left vagal stimulation in pentobarbital-anesthetized animals; 2) tonic left vagal stimulation plus sinus node cooling in pentobarbital-anesthetized animals; and 3) anesthesia with fentanyl, droperidol, and pentobarbital. When tau FR was less than a critical value [1,019 +/- 60 (SE) ms], right vagal stimulus bursts always had the expected negative chronotropic effect. However, when the tau FR was increased beyond critical value, right vagal stimulus bursts delivered within a specific portion of cardiac cycle actually had a positive chronotropic effect; i.e., cycle lengths diminished to values below tau FR. As tau FR was progressively increased beyond critical value, positive chronotropic response became greater and could be evoked by stimulus bursts delivered within a greater fraction of cardiac cycle. The right vagal stimuli that elicited the maximum positive chronotropic effect were those that were given approximately 235 ms prior to beginning of next atrial depolarization. This critical time probably occurs near the end of the period of phase 4 depolarization of sinus node automatic cells.

scholarly journals Antiapolipoprotein A-1 IgG Chronotropic Effects Require Nongenomic Action of Aldosterone on L-Type Calcium Channels

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1269-1278 ◽  
Author(s):  
Michel F. Rossier ◽  
Sabrina Pagano ◽  
Magaly Python ◽  
Andres D. Maturana ◽  
Richard W. James ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Calcium Channels ◽  
Protein Kinase A ◽  
Neonatal Rat ◽  
Chronotropic Effect ◽  
Chronotropic Response ◽  
Nongenomic Action ◽  
Chronotropic Effects ◽  
Spontaneous Contractions ◽  
Kinase A

Autoantibodies to apolipoprotein A-1 (antiapoA-1 IgG) have been shown to be associated with higher resting heart rate and morbidity in myocardial infarction patients and to behave as a chronotropic agent in the presence of aldosterone on isolated neonatal rat ventricular cardiomyocytes (NRVC). We aimed at identifying the pathways accounting for this aldosterone-dependent antiapoA-1 IgG-positive chronotropic effect on NRVC. The rate of regular spontaneous contractions was determined on NRVC in the presence of different steroid hormones and antagonists. AntiapoA-1 IgG chronotropic response was maximal within 20 min and observed only in aldosterone-pretreated cells but not in those exposed to other steroids. The positive antiapoA-1 IgG chronotropic effect was already significant after 5 min aldosterone preincubation, was dependent on 3-kinase and protein kinase A activities, was not inhibited by actinomycin D, and was fully abrogated by eplerenone (but not by spironolactone), demonstrating the dependence on a nongenomic action of aldosterone elicited through the mineralocorticoid receptor (MR). Under oxidative conditions (but not under normal redox state), corticosterone mimicked the permissive action of aldosterone on the antiapoA-1 IgG chronotropic response. Pharmacological and patch-clamp studies identified L-type calcium channels as crucial effectors of antiapoA-1 IgG chronotropic action, involving two converging pathways that increase the channel activity. The first one involves the rapid, nongenomic activation of the phosphatidylinositol 3-kinase enzyme by MR, and the second one requires a constitutive basal protein kinase A activity. In conclusion, our results indicate that, on NRVC, the aldosterone-dependent chronotropic effects of antiapoA-1 IgG involve the nongenomic activation of L-type calcium channels.

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