Biomedical subjects

B Crozatier

Publications and source records attributed to B Crozatier.

At least 37 records · Page 2Linked to original sources

PubMed1996

Stretch-induced modifications of myocardial performance: from ventricular function to cellular and molecular mechanisms.

The purpose of this review is to give an integrative view of the effect of stretch on the myocardium from ventricular function changes to cellular and molecular mechanisms. The general approach will be to discuss the cellular and molecular events which can explain the findings obtained in the whole ventricle. Following the historical development, the classical analysis of the Starling mechanism and the basis of the length-dependent process are rapidly reviewed. We then analyze in greater detail the recent findings on the mechanisms of length-dependent activation changes in contractile protein affinity for calcium, changes in intracellular calcium release, action potential changes and stretch-activated ion channels and discuss the opposite effects of stretch on ventricular contraction (mainly deactivation shortening and viscoelastic properties of the myocardium). Besides the short-term contractile response to stretch, the longer-term effects of myocardial stretch which lead to ventricular hypertrophy will be also rapidly reviewed.

Animals↗

PubMed1995

Propranolol therapy in experimental heart failure in rabbits improves cardiac response to catecholamines without beta-adrenoceptor up-regulation.

Beta-blockade has been shown to improve cardiac response to catecholamines in heart failure but cellular mechanisms of the improvement are unknown. The effect on left ventricular function of a 14 day propranolol treatment was studied in seven treated and eight non-treated rabbits with experimental heart failure. All animals were subjected to a volume (aortic insufficiency) plus pressure (aortic constriction) overload and were instrumented with a left ventricular catheter and ultrasonic crystals measuring anteroposterior left ventricular diameter. Beta-adrenoceptors were measured using 125I-Cyanopindolol in crude membranes. With isoproterenol, the heart rate was slower in treated rabbits than in non-treated rabbits (p < 0.005) and isoproterenol increased more systolic diameter shortening in treated than in non-treated rabbits (p < 0.05). With norepinephrine, for matched pressures, % delta D increased in the treated group but it did not change in the non-treated group. This improvement of ventricular function was due, in a large part, to an increased diastolic response to norepinephrine: end-diastolic diameter increased in the treated group but not in the non-treated group. In contrast with the improved ventricular response to catecholamines, beta-adrenergic receptor density in the treated group was identical to that of the non-treated group (27.8 fmoles/mg/proteins) and was significantly lower than that of normal rabbits (58.2 fmoles/mg, p < 0.01). The improvement of ventricular response to catecholamines appears to be due to a myocardial protection by propranolol against the toxic effect of catecholamines in heart failure and not, at least in this model, to an up-regulation of beta-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed1995

Differential regulation of G protein expression in rat hearts exposed to chronic hypoxia.

Chronic hypoxia impairs adrenergic responsiveness. A modulation of Gs and/or G1 protein alpha-subunits may be associated with the downregulation of the beta-adrenergic receptors previously found in chronic hypoxia. G protein gene expression and protein level and function in rat hearts exposed to a 30-day hypobaric chronic hypoxia were compared with control rat hearts. No change was observed in G alpha s mRNA levels in either right or left ventricles. In right ventricles, mRNA levels of G alpha i-2 increased by 40% (P < 0.05), but not in left ventricles. In both left and right ventricles, chronic hypoxia did not modify G alpha i-2 and G alpha s protein amounts, but significantly decreased functional activity of G alpha s. In conclusion, gene expression, protein levels of G alpha s and G alpha i-2, and activity of G alpha s do not change in parallel fashion with chronic hypoxia. In chronic hypoxic right ventricles, although the mRNA level of G alpha i-2 is increased, the protein level is unchanged. One potential mechanism of desensitization to catecholamines in chronic hypoxia appears to involve a decreased functional activity of G alpha s in spite of normal mRNA and protein levels.

Animals↗

PubMed1995

Inotropic effects of ouabain and Na, K-ATPase activity in failing rabbit hearts.

Left ventricular (LV) function and Na+, K(+)-ATPase activity were studied in rabbit failing heart (FH) obtained by a double pressure plus volume overload which increased LV/body weight ratio by 58%. Ouabain (10(-6) M) increased peak dP/dt by 69% in control hearts (CH) but not in FH. Na+, K(+)-ATPase activity was similar in FH and in CH but the affinity of Na+, K(+)-ATPase for ouabain was significantly higher in CH than in FH (IC50: 2 microM vs 90 microM). The blunted LV contractile response to ouabain in FH is attributed to a decreased Na+, K(+)-ATPase affinity to ouabain and not to a decreased receptor density.

Animals↗

PubMed1995

Regional alterations of left ventricular contraction and inotropic reserve in conscious dogs with heart failure.

OBJECTIVE: The goal was to examine left ventricular (LV) regional contraction alterations and especially, regional inotropic reserve changes in tachycardia-induced heart failure (HF). METHODS: Eleven dogs were chronically instrumented to measure LV pressure and its first time derivative (LV dP/dt), left atrial and aortic pressures and to measure antero-apical (AS), -basal (BS) and postero-apical (PS) subendocardial segmental contractions by ultrasonic crystals. Dobutamine (5-15 micrograms/kg per min) and left atrial pacing (150-240 beats/min) were performed in the control state (C) and in HF induced by chronic right ventricular pacing (240 beats/min, 3 weeks). RESULTS: In HF, as compared with in C, LV dP/dt max decreased and LV end-diastolic pressure and end-diastolic segmental lengths increased (Ps < 0.005). The percentage of systolic shortening was more depressed in PS (from 21 +/- 1% to 7 +/- 1%, P < 0.001) than in AS and BS (from 24 +/- 1% to 17 +/- 1% and from 20 +/- 2% to 13 +/- 1% respectively, Ps < 0.05). During dobutamine infusion, in HF as compared with C, the increases in LV dP/dt max were smaller (dobutamine 15 micrograms/kg per min: HF: + 36 +/- 6% vs C: + 68 +/- 11%, P < 0.01) and the increases in the systolic shortening of the three segments were also smaller. However, the responses of the three segments were similar in HF and in C. During left atrial pacing, LV dP/dt max increased less in HF than in C and the poststimulation potentiation of LV dP/dt max was impaired in HF. However, the responses of the systolic shortening during regular left atrial pacing and the increase in the percentage of systolic shortening of the first poststimulation beat were similar in all regions. CONCLUSION: In tachycardia-induced HF, although LV regional contraction is heterogeneously altered, the inotropic reserve appears to be similarly modified in all regions.

Analysis of Variance↗

PubMed1994

Effects of the calcium channel blockers, diltiazem and Ro 40-5967, on systemic haemodynamics and plasma noradrenaline levels in conscious dogs with pacing-induced heart failure.

1. Calcium channel blockers increase cardiovascular morbidity and mortality in patients with left ventricular dysfunction. These adverse effects are probably related to the negative inotropic effect of calcium channel blockers and/or a neurohormonal activation. 2. The present study was designed to examine, in conscious dogs, the acute haemodynamic and sympathetic effects of diltiazem and Ro 40-5967 (a novel calcium channel blocker) in the control state and in heart failure. 3. Thirteen dogs were instrumented with a micromanometer and an aortic catheter. After completion of experiments in the control state, heart failure was induced by right ventricular pacing (250 beats min-1, 3 weeks). Diltiazem and Ro 40-5967 were given intravenously (0.8 mg kg-1 and 1.0 mg kg-1 respectively). Cardiac output was measured by a thermodilution technique. 4. In the control state, both agents decreased similarly mean aortic pressure with significant increases in heart rate, cardiac output (both +1.0 l min-1 and P < 0.001) and plasma noradrenaline (both +55%) without changes in left ventricular dP/dtmax. In heart failure, for matched decreases in mean aortic pressure, neither diltiazem nor Ro 40-5967 changed heart rate significantly; diltiazem decreased cardiac output (-0.3 l min-1, P < 0.02) and dP/dtmax (-14%, P < 0.001) while Ro 40-5967 still increased cardiac output (+0.3 l min-1, P < 0.02) although the increased amount was smaller than in the control state. Plasma noradrenaline level was increased more during diltiazem infusion (+120%) than during Ro 40-5967 infusion (+38%, P < 0.001). 5. Diltiazem and Ro 40-5967 have similar haemodynamic and sympathetic effects in the control state.Heart failure alters haemodynamic and sympathetic responses to both calcium channel blockers but the magnitude of the alteration appears to be different. Diltiazem exerts a depressant effect on cardiac function which cannot be overcome by its vasodilator effect and sympathetic stimulation, while Ro 40-5967 has little effect on cardiac function. These data suggest that novel calcium channel blockers with less depressant effect may not be detrimental in heart failure.

Animals↗

PubMed1994

Timing and velocity of ejection as major determinants of end-systolic pressure in isolated rabbit hearts.

BACKGROUND: Systolic shortening is known to produce muscle deactivation. The present study was designed to analyze whether the velocity and the timing of ejection play a role on end-systolic pressure-volume relations (ESPVR). METHODS AND RESULTS: In isolated rabbit hearts, left ventricular pressure and volume were recorded and digitized, and left ventricular volume was controlled by a servosystem (4-millisecond cycles) to alter the timing of ejection. A significant deficit in end-systolic pressure was observed when ejection was late in systole with respect to earlier ejection. This was associated with a significantly reduced end-systolic elastance. End-systolic pressure of beats with slow ejection was intermediate between that of the beats with early ejection and that of beats with late ejection with a significantly increased end-systolic volume compared with beats with early rapid ejection. The same results were obtained with hypertrophied hearts (abdominal aortic stenosis). Pressure-volume loop areas were significantly increased in beats with slow ejections and with rapid delayed ejections versus early rapid ejections. No change in the positive peak of dP/dt was observed when the timing and the velocity of ejection were modified. CONCLUSIONS: ESPVR is modified by the ejection profile, with a decreased end-systolic pressure and an increased pressure-volume loop area related to the velocity and the amount of shortening during the end-systolic phase. These indices of ventricular function thus must be used with caution when the timing of ejection is altered, and the end-diastolic volume-peak dP/dt relation may be a better index of ventricular function.

Animals↗

PubMed1994

Sarcoplasmic reticulum function abnormalities in rabbit failing hearts.

In a model of heart failure induced in rabbits by a double volume plus pressure overload, sarcoplasmic reticulum (SR) function was measured by Ca uptake and ryanodine receptor analysis. When expressed per mg of proteins, Ca uptake was decreased by 20% in failing hearts (FH) and ryanodine receptor density was similar in control hearts (CH) and in FH. However Ca uptake and ryanodine receptor density were significantly increased when expressed per total left ventricle suggesting SR hypertrophy. On electron microscopic examination, SR morphology not directly examined but large hypertrophied T tubules were observed suggesting a change in the relationship between membranes and contractile apparatus which may lead to alterations in excitation-contraction-relaxation coupling in spite of minimal biochemical alterations of SR.

Animals↗

PubMed1993

Stretch-induced inositol trisphosphate and tetrakisphosphate production in rat cardiomyocytes.

The kinetics and signal transduction of inositol phosphate production were studied after a 20% stretch of neonatal rat cardiomyocytes in culture. Inositol trisphosphate (IP3) production was increased by 41% above control after 10-20 s of cellular stretch but returned to control after 120 s of stretch. The increase in IP3 was potentiated in high K+ medium and was inhibited by pertussis toxin, suggesting the existence of a pertussis toxin-sensitive G protein in signal transduction. Ion-pair HPLC analysis of cell extracts stretched for 20 s showed an increase in both IP3 isomers, mostly 1,4,5-IP3 (+66%) with a weak increase in IP4 (+10%), whereas 120 s stretch induced an increase in IP4 (+26% above control) associated with a decrease of 1,4,5-IP3 isomer as compared with 20 s stretch. It is concluded that the progressive increase in IP4 production associated with an early rise in IP3 after stretching myocardial cells may be a factor inducing the length-dependent activation of cardiac muscle through a modulation of intracellular free calcium concentration.

Animals↗

PubMed1993

Glomerular atrial natriuretic factor receptors in experimental congestive heart failure.

Heart failure is usually characterized by a relative insensitivity to atrial natriuretic factor (ANF). Downregulation of ANF receptors has been reported but remains controversial. Renal response to ANF infusion, glomerular ANF receptors, and guanosine 3',5'-cyclic monophosphate (cGMP) production have been studied in rabbits with congestive heart failure (CHF) after traumatic aortic regurgitation and abdominal aortic stenosis. Diuresis and natriuresis induced by ANF infusions were significantly decreased in CHF animals. Plasma cGMP was higher in CHF rabbits before ANF administration than in controls (37.6 +/- 7.2 vs. 17.1 +/- 3.9 pmol/ml, P < 0.02) and increased to a same level after ANF in both groups (48.8 +/- 4.2 vs. 52.5 +/- 2.8 pmol/ml, NS). No difference was found in glomerular ANF receptor density (436 +/- 54 vs. 425 +/- 57 fmol/mg protein, NS) nor in affinity between the two groups (dissociation constant; 240 +/- 24 vs. 347 +/- 49 pM, NS). Moreover, in vitro glomerular cGMP production in response to exogenous ANF was preserved. In conclusion, despite a blunted renal response to ANF in vivo, glomerular ANF receptors were unchanged in this model, and no defect in cGMP production in response to ANF was found. This suggests the existence of an intracellular defect beyond the second messenger.

Animals↗

PubMed1993

Hypoxia-induced differential modulation of adenosinergic and muscarinic receptors in rat heart.

To better understand the decreased chronotropic response to catecholamines in chronic hypoxia, we compared the inhibitory pathways regulating adenylate cyclase in rats exposed for 30 days to hypobaric hypoxia (380 Torr; HX) with those in control rats (CT) by the analysis of adenosinergic A1-receptors (8-cyclopentyl-1,3-[3H]dipropylxanthine) and muscarinic M2-receptors ([3H]quinuclidinyl benzilate). A1-receptor density was decreased by 46% in sarcolemmal preparations without a change in the affinity for agonist [(R)-phenylisopropyladenosine]. M2-receptor density was increased (HX: 280 +/- 16 fmol/mg, CT: 188 +/- 15 fmol/mg; n = 7; P < 0.001) without a change in dissociation constant. Displacement of [3H]quinuclidinyl benzilate by carbachol indicated significant decreases in the dissociation constants of both superhigh- (HX: 73 +/- 19 nM, CT: 182 +/- 42 nM; P < 0.001) and high-affinity binding sites (HX: 4 +/- 1 microM, CT: 12 +/- 3 microM; P < 0.001). Our data show that chronic hypoxia leads to differential modulation of cardiac receptors with a downregulation of adenosine receptors and increases in muscarinic receptor affinity and density, which may contribute to the blunted responsiveness of the heart to catecholamines.

Animals↗

PubMed1993

Assessment of coronary reserve in man: comparison between positron emission tomography with oxygen-15-labeled water and intracoronary Doppler technique.

This study compared positron emission tomography (PET) using oxygen-15-labeled water for measurement of coronary reserve with intracoronary Doppler in patients with left anterior descending artery stenosis and patients with no coronary lesion and a coronary reserve 3 as assessed by the invasive technique. To determine whether PET measurement of coronary reserve is altered by partial volume effect, patients with left ventricular dysfunction due to idiopathic cardiomyopathy were studied with both techniques. Direct ultrasonic measurement of coronary reserve was performed the day prior to the PET study: a Doppler catheter was placed in the proximal left anterior descending artery; mean velocity was recorded at baseline and after dipyridamole administration. Using a time-of-flight PET system, patients underwent: (1) an intravenous bolus of oxygen-15-labeled water at baseline and 4 to 6 min after intravenous infusion of dipyridamole using the same protocol as for Doppler study and (2) a 18F-fluorodeoxyglucose (FDG) myocardial imaging. Oxygen-15 time-activity curves were recorded in myocardial regions of interest (ROIs) drawn on a static FDG image. Using the left ventricular time-activity curve as an input function, a standard model with a single-tissue compartment was fitted to the PET data; myocardial blood flow was estimated as the blood-to-tissue transfer rate constant. Coronary reserve measured by PET was well correlated with the measured by intracoronary Doppler (r = 0.98, p < 0.001 for global population). This PET method is an accurate and reliable tool to noninvasively measure coronary reserve in patients, even in those with left ventricular dysfunction.

Blood Flow Velocity↗

PubMed1992

Limited left ventricular inotropic response to exercise in early phase of pressure overload in dogs.

To study the mechanisms of myocardial adaptation to increased stress in the early phase of left ventricular (LV) pressure overload, 12 dogs were instrumented with LV micromanometer, LV dimensional ultrasonic crystals, aortic catheter, and aortic occluder cuff. After recovery, animals performed graded exercise with acute aortic stenosis (AS) or sustained (24 h) aortic stenosis (SS). At baseline, LV functional parameters with SS were not different from those obtained with AS. LV peak pressure increased similarly during exercise with AS or SS, but LV peak dP/dt was lower with SS than with AS (peak values, 6,292 +/- 525 vs. 7,570 +/- 432 mmHg/s; P < 0.05). LV end-diastolic pressure increased from 9.7 +/- 1.7 to 21.4 +/- 3.3 mmHg (P < 0.05) during exercise with SS, but was unchanged with AS. The decrease of the time constant of isovolumic pressure fall during exercise was significantly smaller after SS than during AS (P < 0.05). In addition, the percentage of subendocardial wall thickening did not increase during exercise with SS (30.3 +/- 3.6%), while it increased significantly with AS (from 29.3 +/- 3.3 to 39.4 +/- 4.5%; P < 0.01). Plasma catecholamine levels were similar at baseline and increased to similar levels during exercise with AS and SS. In the early phase of pressure overload, we conclude that exercise capacity is maintained but that the LV inotropic response to exercise is modified with an altered relaxation process and a lesser utilization of subendocardial inotropic reserve.

Animals↗

PubMed1992

Force-frequency relations and response to ryanodine in failing rabbit hearts.

Force-frequency relations were studied in an isolated-perfused rabbit heart model. Heart failure was induced by a double volume plus pressure overload. Studies were performed at the early stage of heart failure when basal ventricular function was not decreased. The normal positive staircase induced by pacing in control hearts (CH) was replaced by a negative staircase in failing hearts (FH) with an increase in end-diastolic pressure for increased heart rates in FH. Postpacing potentiation and postextrasystolic potentiation (PESP) were significantly reduced in FH as compared with CH. Ventricular function decreased by 60% in both CH and FH under ryanodine with similar dose-response curves. Postpacing and PESP disappeared under ryanodine in CH and in FH with a reversal of the negative staircase in FH. The abnormal force-frequency relations observed in heart failure are thus attributed to sarcoplasmic reticulum dysfunction. Basal ventricular function during spontaneous heart rate may be normal in the early stage of heart failure, but sarcoplasmic reticulum dysfunction produces abnormalities in ventricular function when heart rate is abruptly modified, particularly during tachycardia.

Animals↗

PubMed1992

Hypoxia-induced downregulation of beta-adrenergic receptors in rat heart.

To test the desensitization hypothesis of cardiac beta-adrenergic receptors (beta-AR) in chronic hypoxia, the effect of 1, 3, 7, 15, and 21 days of exposure to hypobaric hypoxia (380 Torr) was evaluated in Wistar rats. Exposure to hypoxia for 1-15 days did not induce any change in right and left ventricular beta-AR density (Bmax) determined with [125I]iodocyanopindolol or in antagonist affinity. After 21 days, Bmax decreased by 24% in the left ventricle. In contrast, no change in beta-AR was shown in the right hypertrophied ventricle. Agonist affinity in the left ventricle was not altered, as shown by the analysis of displacement curves of isoproterenol (normoxia 185 +/- 26 nM, hypoxia 170 +/- 11 nM). Moreover, there was no significant decrease in adenylate cyclase activity (pmol.mg-1.min-1) in the left ventricle. In the right ventricle, a 21-day exposure to hypoxia led to a decrease in basal and maximal activity when stimulated by isoproterenol. A decrease in tissue norepinephrine content was observed after 7 days of hypoxia. In conclusion, these data support the beta-AR downregulation hypothesis as one of the mechanisms of myocardial adaptation to high altitude occurring after 2-3 wk of exposure to hypoxia. The regulation pathways of beta-AR may differ between left nonhypertrophied and right hypertrophied ventricles. No evidence of profound abnormality of signal transduction was shown.

Adenylyl Cyclases↗

PubMed1991

Beta-adrenoceptors and adenylate cyclase activity in hypertrophied and failing rabbit left ventricle.

Beta-adrenoceptor density and affinity, studied by H3-CGP 12177 binding, and adenylate cyclase activity were measured in 12 left ventricles of rabbits with heart failure and compared to 13 left ventricles of control (C) rabbits. Heart failure (HF) was induced by a double volume (aortic insufficiency) plus pressure (aortic stenosis 14 days later) overload. Left ventricular mass was increased in HF by 67% above C. Saturation curves with CGP 12177 showed a 36% decrease in beta-adrenoceptor density (C = 61.5 +/- 5.4 fmol/mg prot., P less than 0.05) but competition curves with isoproterenol were not different in HF and C. Basal and Gpp(NH)p stimulated adenylate cyclase activity were decreased by 36% and 22% respectively in rabbits with heart failure as compared with control animals and cAMP production was significantly smaller in failing left ventricles than in control left ventricles both after NaF stimulation (C: 161.3 +/- 24.9 pmols/mg/min; HF: 98.8 +/- 7.0 pmols/mg/min; P less than 0.05) and even more after forskolin stimulation (C: 159.1 +/- 23.9 and HF: 60.8 +/- 7.3 pmols/mg/min; P less than 0.01). Although isoproterenol stimulated ACA was smaller in HF than in C, EC50 was similar in both groups (1.6 x 10(-7) M). We conclude that in the early stage of heart failure in the rabbit, although adrenoceptor density is decreased, there are no changes of affinity of beta-adrenoceptors for isoproterenol and the major alteration of cAMP production appears to lie down-stream the receptor level with a markedly impaired stimulation of adenylate cyclase activity by forskolin.

Adenylyl Cyclases↗

PubMed1991

Loading determinants of isovolumic pressure fall in closed-chest dogs.

The respective roles of load level and loading sequence of the left ventricle (LV) are controversial in the in situ heart. They were analyzed under autonomic blockade and sedation in 17 dogs previously instrumented with a pressure micromanometer and ultrasonic crystals measuring LV diameters and wall thickness for computation of LV volume and stress. The time constant of isovolumic pressure fall (T) and end-systolic pressure (ESP) were calculated during the control state, caval occlusion, aortic constriction obtained by inflation of a hydraulic cuff occluder positioned around the aorta, and during the inflation of an intra-aortic balloon. Caval occlusion significantly decreased both ESP (from 124.0 +/- 6.6 to 88.7 +/- 3.7 mmHg; P less than 0.005) and T (from 29.0 +/- 2.2 to 18.8 +/- 2.4 ms; P less than 0.005), which were linearly correlated (mean r = 0.90 +/- 0.03) and inflation of an intra-aortic balloon increased both ESP (from 107.3 +/- 7.1 to 150.6 +/- 10.4 mmHg; P less than 0.005) and T (from 24.6 +/- 2.1 to 32.7 +/- 2.3 ms; P less than 0.005). Both interventions did not modify the loading sequence (analyzed by the evolution of systolic wall stress vs. time). In contrast, aortic constriction delayed to midsystole the time to which wall stress reached its peak and, for matched ESP with intra-aortic balloon inflation, T was not significantly different from control. We conclude that both the level of afterload and the loading sequence of LV are the determinants of T when contractility is not modified.

Animals↗

PubMed1991

Species differences in myocardial beta-adrenergic receptor regulation in response to hyperthyroidism.

The coupling between myocardial beta-adrenergic receptors, adenylate cyclase activity, and the in vivo cardiac response to catecholamines is controversial in hyperthyroidism. The possibility of species differences in beta-adrenoceptor regulation after thyroxine treatment was studied in dogs and in rats. In dogs instrumented with a left ventricular (LV) pressure micromanometer, hyperthyroidism was induced by L-thyroxine (0.5 mg/kg/day i.v. for 10 days). After hyperthyroidism, heart rate was increased to 167 +/- 10 beats/min (control, 107 +/- 8 beats/min; p less than 0.005) with an increase of peak LV dP/dt from 4,243 +/- 471 to 6,105 +/- 862 mm Hg/sec (p less than 0.01). LV response to injection of increasing doses of isoproterenol and dobutamine was not significantly different before and after induction of the hyperthyroid state, as shown by the unchanged slopes of the LV peak dP/dt versus the log of the dose of isoproterenol and dobutamine. Bmax of beta-receptors measured in crude membranes using 3H-CGP 12177 and in homogenates using 125I-cyanopindolol was not increased in hyperthyroid animals as compared with a control group. Basal adenylate cyclase activity was not different in control and hyperthyroid dogs (32 +/- 3 versus 29 +/- 3 pmol/mg/min), and maximal adenylate cyclase activity response to isoproterenol was similar in control and hyperthyroid dogs. In contrast, in rats subjected to hyperthyroidism (0.5 mg/kg/day i.p. L-thyroxine for 10 days), Bmax of adrenoceptors measured using the same methods was significantly increased as compared with control (+72.5% using 3H-CGP 12177 and +41% using 125I-cyanopindolol, but adenylate cyclase activity was not increased in hyperthyroid rats. We conclude that both adenylate cyclase activity and LV response to catecholamines are not increased by thyroxine-induced hyperthyroidism in dogs and that, in contrast with rats, beta-adrenergic density is not increased in hyperthyroid dogs. This indicates a species difference in myocardial beta-adrenoceptor regulation in response to hyperthyroidism.

Adenylyl Cyclases↗