1 Activation by CGP 12177 and cyanopindolol of the human and rat low-affinity state of beta(1)-adrenoceptors increases frequency and contractile force and hastens relaxation in isolated cardiac tissues, and probably relaxes isolated vessels. In order to identify the positive inotropic, positive lusitropic and vasodilator effects of both agonists also in vivo, we have determined their effects on the left ventricular systolic pressure (LVSP), the rate of intraventricular pressure rise (+dP dt(-1)(max)) and decline (-dP dt(-1)(max)), the diastolic blood pressure (DBP) and the mesenteric blood flow (MBF) in pithed and vagotomized rats. 2 CGP 12177 (0.1-100 nmol kg(-1)) and cyanopindolol (1-1000 nmol kg(-1)) dose-dependently enhanced all cardiac parameters. The nonselective beta-adrenoceptor antagonist bupranolol 10 micromol kg(-1) diminished the CGP 12177 (100 nmol kg(-1))-stimulated increases in LVSP from 26.3+/-8.2 to 13.1+/-1.8 mmHg (P<0.05), +dP dt(-1)(max) from 5287+/-290 to 2439+/-296 mmHg s(-1) (P<0.001) and -dP dt(-1)(max) from -3836+/-301 to -2187+/-443 mmHg s(-1) (P<0.05), respectively. The beta(1)-adrenoceptor antagonist CGP 20712A 10 micromol kg(-1) (known to block the low-affinity state of beta(1)-adrenoceptors at high doses) inhibited increases in +/-dP dt(-1)(max) elicited by the highest dose of CGP 12177. 3 The highest doses of CGP 12177 and cyanopindolol increased DBP by about 10 mmHg and MBF by 1.4+/-0.3 and 0.6+/-0.3 ml min(-1), respectively. The vascular effects of CGP 12177 were not affected by bupranolol and CGP 20712A. 4 In conclusion, activation of the low-affinity state of beta(1)-adrenoceptors by CGP 12177 and cyanopindolol in pithed rats causes a positive inotropic and lusitropic effect. By contrast, the vascular effects of CGP 12177 and cyanopindolol are not mediated by these receptors and have only marginal influence under in vivo conditions.
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http://dx.doi.org/10.1038/sj.bjp.0706382 | DOI Listing |
Clin Exp Pharmacol Physiol
November 2021
Department of Experimental Physiology and Pathophysiology, Medical University of Białystok, Białystok, Poland.
We have previously shown that cannabinoid CB and CB receptor antagonists, AM251 and AM630, respectively, modulate cardiostimulatory effects of isoprenaline in atria of Wistar rats. The aim of the present study was to examine whether such modulatory effects can also be observed (a) in the human atrium and (b) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Inotropic effects of isoprenaline and/or CGP12177 (that activate the high- and low-affinity site of β -adrenoceptors, respectively) were examined in paced human atrial trabeculae and rat left atria; chronotropic effects were studied in spontaneously beating right rat atria.
View Article and Find Full Text PDFJ Nucl Med
July 2021
Department of Cardiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
The mechanism of chronotropic incompetence (CTI), which has been associated with autonomic dysfunction, has not been elucidated in patients without heart failure (HF). Cardiac PET using C-CGP12177 was performed to investigate the cardiac β-adrenergic receptor density (β-ARD) in 13 patients with CTI without HF and 6 healthy controls. The maximum number of available specific C-CGP12177 binding sites per gram of tissue was calculated in regions of interest using an established graphical method.
View Article and Find Full Text PDFBiol Pharm Bull
September 2020
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
Life Sci
January 2020
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University, Miyama 2-2-1, Funabashi-City, Chiba 274-8510, Japan. Electronic address:
Aims: β-Adrenoceptors (β-ADRs) mediating the relaxation of rat superior mesenteric arteries (SMAs) were pharmacologically identified, and the effects of chemical sympathetic denervation on β-ADR-mediated relaxation were examined.
Main Methods: The tension changes of endothelium-denuded SMAs were isometrically recorded and the mRNA of endothelium-denuded SMA β-ADR was detected using RT-PCR.
Key Findings: In endothelium-denuded SMAs contracted with ≥10 M phenylephrine (an α-ADR agonist), isoprenaline (a β-ADR agonist)-induced relaxation was competitively inhibited by 3 × 10-10 M propranolol (a β-ADR antagonist), but not further affected by ≥10 M propranolol.
Addict Biol
July 2019
Translational Research Institute, Queensland University of Technology, Brisbane, Australia.
Repeated cycles of binge-like alcohol consumption and abstinence change the activity of several neurotransmitter systems. Some of these changes are consolidated following prolonged alcohol use and are thought to play an important role in the development of dependence. We have previously shown that systemic administration of the dual beta-adrenergic antagonist and 5-HT partial agonist pindolol selectively reduces long-term but not short-term binge-like consumption of ethanol and alters excitatory postsynaptic currents in basolateral amygdala (BLA) principal neurons.
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