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The Role of Acute and Long‐Term Use of Cannabinoids on Hypertension and Kidney Injury
Author(s) -
Golosova Daria,
Levchenko Vladislav,
Palygin Oleg,
Staruschenko Alexander
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02043
Subject(s) - anandamide , blood pressure , medicine , endocannabinoid system , cannabinoid , cannabinoid receptor , kidney , endocrinology , pharmacology , receptor , antagonist
The endocannabinoid system is present in many tissues, including the kidney, and could play a prominent role in regulating renal homeostasis in health and disease. Cannabinoids and their endogenous and synthetic analogs may alter blood pressure and contribute to the incidence of hypertension. The amide of arachidonic acid ‐ arachidonoyl ethanolamide or anandamide (AEA) is an important signaling compound synthesized by the body which binds to the cannabinoid receptors and activates the corresponding G‐protein signal cascade. Here we explore the activation of cannabinoid receptors (CB1 or CB2) with AEA and the possibility of modulation of renal function and blood pressure under conditions of salt‐induced hypertension in Dahl Salt‐Sensitive (SS) rats. This study aimed to test acute and chronic effects of AEA in vivo in conscious Dahl SS rats on normal salt (0.4% NaCl, NS) or high salt (8% NaCl, HS) diets. The femoral artery and vein of 8‐week old male SS rats were catheterized under anesthesia. The arterial catheter was connected to a pressure transducer for arterial blood pressure acquisition and venous catheter was used for daily intravenous bolus drug infusion. Rats were treated with the drug (AEA, 0.05 or 3 mg/kg/day) or a corresponding vehicle for the whole duration of the experiment after a surgical recovery. At the end of the protocol, animals were euthanized, and blood and kidney tissues were harvested for the following analyses. We demonstrated that acute application of either a low or a high dose of AEA (0.05 or 3 mg/kg/day) under NS diet did not affect blood pressure (up to 2 hrs after an injection). Chronic administration of a low dose of AEA (rats were switched to a HS diet for 14 days) had no effects on blood pressure and kidney injury. However, a high dose of AEA led to a significant aggravation of hypertension (152±6 vs. 168±4 mmHg, p<0.05 compared to vehicle) and a profound interstitial fibrosis. The Western blot analyses revealed reduced expression of CB2 receptors in the renal cortex following chronic AEA treatment, which may play a crucial role in developing of hypertension during the HS challenge. Additionally, urinary electrolyte analyses (24 hrs collection) revealed increased sodium and chloride excretions (287±19 vs. 365±23, Na + /Cre ratio; 279±15 vs. 370±31, Cl ‐ /Cre ratio, p<0.05 compared to vehicle) in hypertensive rats chronically treated with the high dose of AEA. We may collectively speculate that the endocannabinoid system's prolonged stimulation promoted renal interstitial fibrosis via the loss of CB2 receptors and contributed to the aggravation of salt‐induced hypertension.