Angiotensin II-Induced Cardiac Effects Are Modulated by Endocannabinoid-Mediated CB 1 Receptor Activation

• Published in: Cells (Basel, Switzerland) Vol. 10; no. 4
• Main Authors: Miklós, Zsuzsanna, Wafa, Dina, Nádasy, György L, Tóth, Zsuzsanna E, Besztercei, Balázs, Dörnyei, Gabriella, Laska, Zsófia, Benyó, Zoltán, Ivanics, Tamás, Hunyady, László, Szekeres, Mária
• Format: Journal Article
• Language: English
• Published: Switzerland 24-03-2021
• Subjects: Angiotensin II - pharmacology; Animals; Arachidonic Acids - pharmacology; Coronary Circulation - drug effects; Endocannabinoids - metabolism; Endocannabinoids - pharmacology; Glycerides - pharmacology; Heart - drug effects; Lipoprotein Lipase - antagonists & inhibitors; Lipoprotein Lipase - metabolism; Male; Myocardial Contraction - drug effects; Orlistat - pharmacology; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1 - agonists; Receptor, Cannabinoid, CB1 - antagonists & inhibitors; Receptor, Cannabinoid, CB1 - metabolism; CB1 cannabinoid receptor; endocannabinoid; coronary flow; myocardial function; vasoconstriction; Angiotensin II; cardiac
• ISSN: 2073-4409

Angiotensin II (Ang II) has various cardiac effects and causes vasoconstriction. Ang II activates the type-1 angiotensin receptor-G
signaling pathway resulting in the release of 2-arachidonoylglycerol (2-AG). We aimed to investigate whether cardiac Ang II effects are modulated by 2-AG-release and to identify the role of type-1 cannabinoid receptors (CB
R) in these effects. Expression of CB
R in rat cardiac tissue was confirmed by immunohistochemistry. To characterize short-term Ang II effects, increasing concentrations of Ang II (10
-10
M); whereas to assess tachyphylaxis, repeated infusions of Ang II (10
M) were administered to isolated Langendorff-perfused rat hearts. Ang II infusions caused a decrease in coronary flow and ventricular inotropy, which was more pronounced during the first administration. CB agonist 2-AG and WIN55,212-2 administration to the perfusate enhanced coronary flow. The flow-reducing effect of Ang II was moderated in the presence of CB
R blocker O2050 and diacylglycerol-lipase inhibitor Orlistat. Our findings indicate that Ang II-induced cardiac effects are modulated by simultaneous CB
R-activation, most likely due to 2-AG-release during Ang II signalling. In this combined effect, the response to 2-AG via cardiac CB
R may counteract the positive inotropic effect of Ang II, which may decrease metabolic demand and augment Ang II-induced coronary vasoconstriction.