Dissociation between positive inotropic and alkalinizing effects of angiotensin II in feline myocardium

1997 ◽  
Vol 272 (3) ◽  
pp. H1131-H1136 ◽  
Author(s):  
A. Mattiazzi ◽  
N. G. Perez ◽  
M. G. Vila-Petroff ◽  
B. Alvarez ◽  
M. C. Camilion de Hurtado ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Simultaneous Measurement ◽  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Ang Ii ◽  
Acetoxymethyl Ester ◽  
Hepes Buffer ◽  
Ethanesulfonic Acid

The present study examines the intracellular pH (pHi) dependence of angiotensin (ANG) II-induced positive inotropic effect in cat papillary muscles contracting isometrically (0.2 Hz, 30 degrees C). Muscles were loaded with the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester for simultaneous measurement of pHi and contractility. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer (n = 4), there was a temporal dissociation between the positive inotropic and the alkalinizing effects of ANG II (0.5 microM). The positive inotropic effect of ANG II peaked at 9.7 +/- 0.8 min (240 +/- 57% above control) without significant changes in pHi. The increase in pHi became significant (0.05 +/- 0.01 pH units) only after 16 min of exposure to the drug, when the positive inotropic effect of ANG II was already fading. In HCO3- buffer (n = 7), the ANG II-induced positive inotropic effect occurred without significant pHi changes. In the presence of 5 microM ethyl isopropyl amiloride (EIPA, to specifically inhibit the Na+/H+ exchanger), the alkalinizing effect of ANG II was changed to a significant decrease in pHi, despite which ANG II still increased contractility by 87 +/- 16% (n = 6). The results indicate that in HEPES buffer only a fraction of the ANG II-induced positive inotropic effect can be attributed to a pHi change, whereas in a physiological CO2-HCO3- medium the positive inotropic effect of ANG II is independent of pHi changes. Furthermore, an ANG II-induced increase in myocardial contractility was observed even when ANG II administration elicited a decrease in pHi, as occurred after Na+/H+ exchanger blockade. The results show that in feline myocardium, the increase in contractility evoked by ANG II in a physiological CO2-HCO3- medium is not due to an increase in Ca2+ myofilament sensitivity secondary to an increase in myocardial pHi.

Alpha 1-adrenoceptor subtypes mediating inotropic and electrophysiological effects in mammalian myocardium

1996 ◽  
Vol 271 (4) ◽  
pp. H1423-H1432
Author(s):  
M. Nagashima ◽  
Y. Hattori ◽  
Y. Akaishi ◽  
N. Tohse ◽  
I. Sakuma ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Outward Current ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Transient Outward Current ◽  
Papillary Muscles ◽  
Binding Studies ◽  
Positive Inotropism ◽  
Wb 4101 ◽  
Rabbit Ventricular Myocardium

Stimulation of alpha 1-adrenoceptors produces a positive inotropic effect in rat and rabbit ventricular myocardium via different mechanisms, the prolongation of action potential duration (APD) exclusively in the former and an increase in myofibrillar Ca2+ sensitivity in large part in the latter. This study was designed to determine whether the two inotropic mechanisms are mediated by different alpha 1-adrenoceptor subtypes. In rat papillary muscles, the positive inotropic effect and APD prolongation induced by phenylephrine (in the presence of propranolol) were inhibited by WB-4101, but not affected by chlorethylclonidine (CEC). WB-4101, but not CEC, blocked the phenylephrine-induced inhibition of the transient outward current (Ito) in rat ventricular cells. On the other hand, WB-4101 and CEC each antagonized the positive inotropic effect of phenylephrine in rabbit papillary muscles. However, the phenylephrine-induced APD prolongation observed in rabbit papillary muscles was blocked only by WB-4101. These results indicate that the WB-4101 sensitive alpha 1-adrenoceptor subtype mediates the positive inotropism that is correlated with the APD prolongation resulting from Ito reduction, whereas the CEC-sensitive subtype mediates the positive inotropism that is probably associated with increased myofibrillar Ca2+ sensitivity. Radioligand binding studies with [3H] prazosin showed a similar ratio of alpha 1A-to alpha 1B-adrenoceptor subtypes in rat and rabbit ventricular myocardium, implying that the different degree of contribution of each action mechanism to the overall inotropic effect in the two species cannot be explained by distribution of the alpha 1-adrenoceptor subtypes.

Comparative effect of procainamide and lidocaine on myocardial contractility

1969 ◽  
Vol 47 (12) ◽  
pp. 1038-1042 ◽  
Author(s):  
M. Nahas ◽  
J. Lachapelle ◽  
G. M. Tremblay
Keyword(s):  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Inotropic Effect ◽  
Comparative Effect ◽  
Heart Perfusion ◽  
Biphasic Effect ◽  
Therapeutic Doses

The effect of procainamide and lidocaine on myocardial contractility was studied in an isovolumic isolated rat heart perfusion preparation following the Langendorff technique. As a measure of myocardial contractility, the left ventricular intracavitary pressure and maximum dp/dt were determined and were found to be depressed proportionately to the dose of these agents. At the same concentration, lidocaine showed a more negative inotropic effect than procainamide (although the former seems clinically innocuous at therapeutic doses). In addition, procainamide produced in about one-half of the experiments a biphasic effect characterized by a slight transitory positive inotropic effect followed by a negative inotropic effect.

scholarly journals Reactive oxygen species partially mediate high dose angiotensin II-induced positive inotropic effect in cat ventricular myocytes

2015 ◽  
Vol 24 (4) ◽  
pp. 236-240 ◽  
Author(s):  
Alejandra M. Yeves ◽  
Claudia I. Caldiz ◽  
Ernesto A. Aiello ◽  
María C. Villa-Abrille ◽  
Irene L. Ennis
Keyword(s):  
Reactive Oxygen Species ◽  
Angiotensin Ii ◽  
Positive Inotropic Effect ◽  
Ventricular Myocytes ◽  
Reactive Oxygen ◽  
Inotropic Effect ◽  
High Dose ◽  
Oxygen Species

Evidence for physiological functions of protein phosphatases in the heart: evaluation with okadaic acid

1993 ◽  
Vol 265 (1) ◽  
pp. H257-H266 ◽  
Author(s):  
J. Neumann ◽  
P. Boknik ◽  
S. Herzig ◽  
W. Schmitz ◽  
H. Scholz ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Okadaic Acid ◽  
Guinea Pigs ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Force Of Contraction ◽  
Phosphorylation State ◽  
Ventricular Cardiomyocytes ◽  
Channel Currents

Okadaic acid exerts a positive inotropic effect in cardiac preparations. We studied whether the positive inotropic effect of okadaic acid in cardiac preparations could be due to phosphatase inhibition and whether this inhibition affects the phosphorylation of cardiac proteins. In papillary muscles from guinea pigs, 30 microM okadaic acid increased force of contraction to 175% of predrug value. In isolated guinea pig ventricular cardiomyocytes, okadaic acid augmented single Ca(2+)-channel currents by enhancing channel availability. In homogenates from ventricles, 1 microM okadaic acid completely inhibited phosphorylase a phosphatase activity. In isolated 32P-labeled ventricular cardiomyocytes, 30 microM okadaic acid increased phosphorylation of phospholamban (PLB) and troponin inhibitor (TnI) to 325 and 284% of control, respectively. Furthermore, 30 microM okadaic acid increased phosphorylation of a hitherto unknown 23-kDa protein to 352% of control. It is concluded that the effects of okadaic acid could be mediated by increasing the phosphorylation state of several proteins including PLB, a 23-kDa protein, and TnI.

Effects of angiotensin II and vasopressin on intracellular pH of glomerular mesangial cells

1988 ◽  
Vol 254 (6) ◽  
pp. F787-F794 ◽  
Author(s):  
M. B. Ganz ◽  
G. Boyarsky ◽  
W. F. Boron ◽  
R. B. Sterzel
Keyword(s):  
Angiotensin Ii ◽  
Intracellular Ph ◽  
Mesangial Cells ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Initial Value ◽  
Ph Change ◽  
Acid Load ◽  
Ethanesulfonic Acid ◽  
Acid Extrusion

We investigated changes in intracellular pH (pHi) of cultured rat glomerular mesangial cells (MCs) exposed to angiotensin II (ANG II) and arginine vasopressin (AVP). pHi of quiescent MCs, passage 2–5, and grown on glass cover slips, was assessed by spectrofluorometry using the pH-sensitive dye, 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). The steady-state pHi of MCs in a pH 7.4, HCO3-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution was 7.10 +/- 0.02 (n = 68) and in a pH 7.4, HCO3-containing solution, was 7.23 +/- 0.03 (n = 47) (P less than 0.01). The pHi recovery following an NH+4-induced acid load was inhibited by removal of Na+ from the bath or by addition of the amiloride analogue, ethyl isopropyl amiloride (EIPA). These effects were observed in MCs bathed in HEPES- or in HCO3-buffered solutions, consistent with the action of a Na+-H+ exchanger. When cells were bathed in HEPES, a 10-min exposure to ANG II or AVP (10(-10) to 10(-6) M) caused early and transient acidification of MCs (maximal pH change was -0.10), followed by gradual alkalinization (maximal pHi change +0.15 above the initial value). The increase of pHi was dependent on the presence of Na+ in the bath and was inhibited by EIPA. In the presence of HCO3, ANG II or AVP induced merely a small gradual acidification of MCs (pHi change -0.05). These findings demonstrate that MCs utilize a Na+-H+ exchanger for acid extrusion.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Adenosine inhibits the positive inotropic effect of 3-isobutyl-1-methylxanthine in papillary muscles without effect on cyclic AMP or cyclic GMP

1988 ◽  
Vol 93 (4) ◽  
pp. 729-738 ◽  
Author(s):  
Michael Böhm ◽  
Reinhard Brückner ◽  
Joachim Neumann ◽  
Monika Nose ◽  
Wilhelm Schmitz ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Cyclic Gmp ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles
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