α1a-Adrenergic receptor mediated positive chronotropic effect in right atria isolated from rats

1994 ◽  
Vol 72 (12) ◽  
pp. 1574-1579 ◽  
Author(s):  
Anthony P. Williamson ◽  
Ernst Seifen ◽  
Jon P. Lindemann ◽  
Richard H. Kennedy
Keyword(s):  
Adrenergic Receptor ◽  
Response Curve ◽  
Male Rats ◽  
Chronotropic Effect ◽  
Rightward Shift ◽  
Spontaneous Rate ◽  
Negative Chronotropic Effect ◽  
Right Atria ◽  
Concentration Response Curve ◽  
Positive Chronotropic Effect

Experiments in right atria isolated from adult male rats were designed to determine which of the α1-adrenergic receptor (α1-AR) subtypes are involved in the positive chronotropic effect of phenylephrine, an α1-AR agonist. Chloroethylclonidine (CEC), an irreversible α1b-, α1c-, and α1d-AR antagonist, did not alter the efficacy or potency of phenylephrine; however, CEC did elicit a concentration-dependent negative chronotropic effect and reduce the absolute maximum spontaneous rate observed in the presence of phenylephrine. WB4101, a competitive α1a- and α1c-AR-selective antagonist, did not alter basal spontaneous rate or the efficacy of phenylephrine, but it did produce a significant rightward shift of the phenylephrine concentration–response curve. Phenoxybenzamine, an irreversible nonselective α-AR antagonist, elicited a concentration-dependent negative chronotropic effect, a significant rightward shift of the phenylephrine concentration–response curve, and a reduction in the efficacy of phenylephrine. The chronotropic action of the β-adrenergic agonist isoproterenol was not affected by CEC, WB4101, or phenoxybenzamine. These data suggest that the positive chronotropic effect of α1-adrenergic agonists in rat right atria is mediated via stimulation of α1a-ARs.Key words: α1-adrenergic receptor subtypes, chloroethylclonidine, WB4101, phenylephrine, right atria (rat).

Inhibitory effects of catecholamines in canine cardiac Purkinje fibers

1976 ◽  
Vol 231 (5) ◽  
pp. 1415-1420 ◽  
Author(s):  
P Posner ◽  
EL Farrar ◽  
CR Lambert
Keyword(s):  
Negative Response ◽  
Chronotropic Effect ◽  
Inhibitory Effects ◽  
Purkinje Fibers ◽  
Spontaneous Rate ◽  
Negative Chronotropic Effect ◽  
Cardiac Purkinje Fibers ◽  
Wide Range ◽  
Low Levels

The effect of catecholamines over a wide range of concentrations was studied on 42K uptake and efflux, as well as on spontaneous rate in canine cardiac Purkinje fibers. Low levels of catecholamines (less than 10(-10) M epinephrine; less than 10(-9) M norepinephrine) decreased automaticity. This negative chronotropic effect was blocked by phentolamine and mimicked by phenylephrine. These low levels of epinephrine and norepinephrine also inhibited 42K uptake by Purkinje fibers but had no effect on 42K efflux. The inhibition of 42K uptake was blocked by phentolamine and verapamil and mimicked by phenylephrine. The data indicate an alpha-receptor-mediated negative response of rate and 42K uptake to low levels of catecholamine. The end result is discussed in terms of a competitive increase in the influx of Ca2+ rather than Na+ and an indirect inhibition of the Na+-K+ pump.

Evidence against KATP channel involvement in adenosine receptor-mediated dilation of epicardial vessels

1994 ◽  
Vol 267 (2) ◽  
pp. H716-H724 ◽  
Author(s):  
S. R. Makujina ◽  
H. A. Olanrewaju ◽  
S. J. Mustafa
Keyword(s):  
Adenosine Receptor ◽  
Katp Channel ◽  
Response Curve ◽  
Channel Blocker ◽  
Rightward Shift ◽  
Prostaglandin F2 Alpha ◽  
Phenylisopropyl Adenosine ◽  
Concentration Response Curve ◽  
Channel Activator

The purpose of this study was to determine whether ATP-glyburide-sensitive K+ (KATP-glyburide) channels are involved in the adenosine-induced vasorelaxation of porcine and canine epicardial vessels in vitro. Adenosine and its analogues, 2-chloroadenosine (CAD), 5'-N-ethylcarboxamidoadenosine (NECA), R-N6-(2-phenylisopropyl)adenosine (R-PIA), N6-cyclopentyladenosine (CPA), N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)]adenosine (DPMA), 2-phenylaminoadenosine (CV-1808), 2-[m-(carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine (CGS-22988), 2-[(2-cyclohexylethyl)amino]adenosine (CGS-22492), 2-[(p-amino)phenethylamino]adenosine (APE), and 2-(1-octynyl)adenosine (YT-146) (10 nM-100 microM), produced concentration-dependent relaxations in endothelium-intact and -denuded arterial ring segments contracted with 30 mM KCl, 10 nM endothelin-1, or 10 microM prostaglandin F2 alpha. Sodium nitroprusside (SNP; 1 nM-10 microM) and KATP-channel activator, pinacidil (10 nM-10 microM), also produced similar vasodilatory responses. Glyburide, a KATP-channel blocker, caused a rightward shift of the concentration-response curve to pinacidil but did not alter the responses elicited by SNP or adenosine and its analogues. The data suggest that KATP-glyburide channels are not involved in the mechanism whereby adenosine and its analogues elicit their vasorelaxant response in isolated porcine or canine epicardial vessels.

Functional β2-adrenoceptors in rat left atria: effect of foot-shock stress

2017 ◽  
Vol 95 (9) ◽  
pp. 999-1008 ◽  
Author(s):  
André Luiz de Moura ◽  
Stephen Hyslop ◽  
Dora M. Grassi-Kassisse ◽  
Regina C. Spadari
Keyword(s):  
Receptor Antagonist ◽  
Adenylyl Cyclase ◽  
Left Atrial ◽  
Male Rats ◽  
Inotropic Response ◽  
Chronotropic Effect ◽  
Adenylyl Cyclase Activity ◽  
Altered Sensitivity ◽  
Right Atria ◽  
Shock Stress

Altered sensitivity to the chronotropic effect of catecholamines and a reduction in the β1/β2-adrenoceptor ratio have previously been reported in right atria of stressed rats, human failing heart, and aging. In this report, we investigated whether left atrial inotropism was affected by foot-shock stress. Male rats were submitted to 3 foot-shock sessions and the left atrial inotropic response, adenylyl cyclase activity, and β-adrenoceptor expression were investigated. Left atria of stressed rats were supersensitive to isoprenaline when compared with control rats and this effect was abolished by ICI118,551, a selective β2-receptor antagonist. Schild plot slopes for the antagonism between CGP20712A (a selective β1-receptor antagonist) and isoprenaline differed from unity in atria of stressed but not control rats. Atrial sensitivity to norepinephrine, as well as basal and forskolin- or isoprenaline-stimulated adenylyl cyclase activities were not altered by stress. The effect of isoprenaline on adenylyl cyclase stimulation was partially blocked by ICI118,551 in atrial membranes of stressed rats. These findings indicate that foot-shock stress equally affects inotropism and chronotropism and that β2-adrenoceptor upregulation contributes to the enhanced inotropic response to isoprenaline.

Chronotropic response to (±)-CGP12177 in right atria of stressed rats

2001 ◽  
Vol 79 (5) ◽  
pp. 393-399 ◽  
Author(s):  
I N Santos ◽  
R C Spadari-Bratfisch
Keyword(s):  
Response Curve ◽  
Response Curves ◽  
Stimulant Effect ◽  
Chronotropic Response ◽  
Stress Changes ◽  
Random Intervals ◽  
The Right ◽  
Right Atria ◽  
Concentration Response Curve ◽  
Shock Stress

Foot-shock stress changes the sensitivity of the rat right atria to β1- and β2-adrenoceptor (AR) agonists. We investigated whether the same stress protocol also changes the atrial sensitivity to the non conventional agonist, (±)-CGP12177. Concentration-response curves to (±)-CGP12177, a β1- and β2-adrenoceptor antagonist with agonist properties at the putative β4-adrenoceptors, were obtained in the absence and presence of propranolol (200 nM or 2 µM), CGP20712A 10 nM plus ICI118,551 50 nM, or CGP20712A (1 µM or 3 µM), in right atria from rats submitted to three daily foot-shock sessions (120 mA pulses of 1.0 s duration applied at random intervals of 5-25 s over 30 min) and killed after the third session. The pD2 for (±)-CGP12177 was not influenced by foot-shock stress. The stimulant effect of (±)-CGP12177 was resistant to blockade by 200 nM and 2 µM (±)-propranolol, and to combined blockade by CGP20712A and ICI118,551. However, in right atria from stressed rats given 200 nM propranolol, the concentration-response curve to the agonist was shifted 2.0-fold to the right. CGP20712A shifted the concentration-response curve to (±)-CGP12177 to the right by 4.6- (1 µM) and 19-fold (3 µM) in atria of control rats, and by 2.2- (1 µM) and 43-fold (3 µM) in atria of stressed rats. Maximum response to CGP12177 was not affected by propranolol or CGP20712A in concentrations ranging from 0.1 nM to 10 µM. These results show that the chronotropic effect of (±)-CGP12177 is mediated by atypical β4-adrenoceptors. In constrast with to β1-and (or) β2-AR, this receptor is resistant to the effects of foot-shock stress, suggesting that the putative β4-AR is a different receptor from a low affinity state of β1-adrenoceptor, as previously proposed, unless both proposed isoforms of β1-adrenoceptor show independent stress-induced behavior.Key words: putative β4-adrenoceptor, low affinity β1-adrenoceptor isoform, stress, right atria, chronotropic response.

A specific endothelin-1 antagonist blocks inhaled endothelin-1-induced bronchoconstriction in sheep

1993 ◽  
Vol 74 (5) ◽  
pp. 2537-2542 ◽  
Author(s):  
W. M. Abraham ◽  
A. Ahmed ◽  
A. Cortes ◽  
M. J. Spinella ◽  
A. B. Malik ◽  
...  
Keyword(s):  
Response Curve ◽  
Thrombin Receptor ◽  
Response Curves ◽  
Leukotriene D4 ◽  
Rightward Shift ◽  
Endothelin 1 ◽  
Partial Concentration ◽  
Conscious Sheep ◽  
Relative Potencies ◽  
Concentration Response Curve

In this study we used conscious sheep to compare the relative potencies of inhaled endothelin- (ET) 1 and ET-3 and to determine whether a newly described selective ET-1 receptor antagonist, [diaminopropionic acid1-Asp15]ET-1 ([Dpr1-Asp15]ET-1), when given as an aerosol blocks ET-1-induced bronchoconstriction. Partial concentration-response curves to ET-1 and ET-3 were obtained by measuring the change in pulmonary airflow resistance (RL) after aerosol challenge. Both ET-1 (n = 6) and ET-3 (n = 4) caused concentration-dependent (10(-10)-10(-7) bronchoconstriction, but ET-3 was 400-fold less potent than ET-1. Pretreatment (30 min) with 25 breaths of 5 x 10(-8) M [Dpr1-Asp15]ET-1 caused a 100-fold rightward shift of the ET-1 concentration-response curve. The activity of the ET-1 antagonist (25 breaths of 5 x 10(-8) M) was compared with that of various control peptides (25 breaths of 10(-8) M). ET-1 (50 breaths of 10(-7) M) caused an increase in RL of 133 +/- 33% (SE) over baseline. [Dpr1-Asp15]ET-1 significantly inhibited this response by 54%. No protection was seen with a monocyclic control peptide or a thrombin receptor peptide. There was, however, a small protective effect (38%, P < 0.05) seen with [Dpr1-Asp15]ET-3, a structurally homologous ET-3 antagonist. [Dpr1-Asp15]ET-1 had no effect on carbachol (n = 3) or leukotriene D4-induced bronchoconstriction. Thus inhaled ET-1 and, to a lesser extent, ET-3 cause concentration-dependent bronchoconstriction in conscious sheep.

Involvement of gap junctions in bradykinin-induced relaxation of bovine pulmonary supernumerary arteries before and after inhibition of nitric oxide/guanylate cyclase

2002 ◽  
Vol 103 (6) ◽  
pp. 553-557 ◽  
Author(s):  
A. TRACEY ◽  
A. MACDONALD ◽  
A.M. SHAW
Keyword(s):  
Nitric Oxide ◽  
Gap Junctions ◽  
Guanylate Cyclase ◽  
Response Curve ◽  
Soluble Guanylate Cyclase ◽  
Rightward Shift ◽  
Before And After ◽  
Synthase Inhibitor ◽  
Gap Junction Inhibitor ◽  
Concentration Response Curve

This study evaluated the possible contribution of gap junctions to the nitric oxide (NO)- and endothelium-derived hyperpolarizing factor (EDHF)-mediated responses elicited by bradykinin in bovine pulmonary supernumerary arteries. In artery rings with an intact endothelium and treated with the cyclo-oxygenase inhibitor indomethacin (10μM), bradykinin (100pM–1μM) produced a concentration-dependent relaxation [-logEC50 (pEC50), 9.6±0.2; maximum relaxation (Rmax), 89.7±14.8%; n = 6]. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 100μM) and the NO scavenger hydroxocobalamin (200μM) each produced a rightward shift in the bradykinin concentration–response curve [pEC50: L-NAME, 8.9±0.1 (n = 6; P<0.01); hydroxocobalamin, 8.3±0.2, (n = 6; P<0.001)]. However, the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one; 10μM) did not significantly alter the response to bradykinin (pEC50 9.4±0.2; n = 9). The gap junction inhibitor carbenoxolone (100μM) did not affect the relaxation produced by bradykinin (pEC50, 9.7±0.1; Rmax, 100±3.2%; n = 6), but it significantly depressed Rmax when L-NAME, hydroxocobalamin or ODQ was present. Further, carbenoxolone produced a rightward shift in the bradykinin concentration–response curve in the presence of ODQ (8.4±0.1; n = 6, P<0.01). The data suggest that, in bovine pulmonary supernumerary arteries, gap junctions may, in part, facilitate the EDHF-mediated response, but not the NO-mediated response, to bradykinin. However, the additional involvement of an unidentified endothelial relaxing factor cannot be excluded.

Cholinergic stimulation modulates negative inotropic effect of cocaine on ferret ventricular myocardium

1996 ◽  
Vol 270 (2) ◽  
pp. H678-H684
Author(s):  
L. Miao ◽  
Z. Qiu ◽  
J. P. Morgan
Keyword(s):  
Response Curve ◽  
Negative Inotropic Effect ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Dependent Manner ◽  
Cholinergic Stimulation ◽  
Concentration Dependent Manner ◽  
Cell Shortening ◽  
Inotropic State ◽  
Concentration Response Curve

We tested the hypothesis that the negative inotropic effect (NIE) of cocaine is mediated, at least in part, by cholinergic stimulation and can be correlated with the degree of adenosine 3',5'-cyclic monophosphate (cAMP) dependency of the inotropic state. Cardiac myocytes were isolated from left ventricles of ferrets and loaded with the fluorescent Ca2+ indicator indo 1. Cells were placed in physiological solution containing 2.0 mM Ca2+ and stimulated at 0.5 Hz and 30 degrees C. Cocaine decreased peak cell shortening and peak intracellular Ca2+ in a concentration-dependent manner (10(-8)-10(-4) M). The concentration-response curve of cocaine was shifted significantly downward compared with those of lidocaine and procaine in the same range of concentrations. Atropine (10(-6) M) shifted the concentration-response curve of cocaine, but not those of lidocaine and procaine, rightward, with a pA2 value (7.66) similar to that obtained with carbachol (7.99). With prior addition of isoproterenol (ISO, 10(-8) M) or increased Ca2+ (4.0 mM) to increase cell shortening to the same degree (approximately 60%), cocaine and carbachol decreased contractility to a significantly greater extent in ISO-stimulated myocytes. To clarify whether these treatments changed responsiveness of the contractile elements to Ca2+, the effect of 2,3-butanedione monoxime, an agent that interferes with the interaction of myosin and actin, was tested with previous addition of ISO or increased Ca2+, and no differential effect occurred. Therefore, we postulate that 1) the NIE of cocaine on myocytes is caused by decreased Ca2+ availability; 2) this effect is due to specific stimulation of cholinergic receptors in addition to other direct myocardial (probably local anesthetic) effects; and 3) the NIE correlates with the level of cAMP dependence of the inotropic state.

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