Journal of Hypertension: Open Access

The Effects of Chronic Cannabinoid Administration on the Haematological Parameters, Oxidative Stress, BNP, and the Gene Expression of TNF?A in a Rat Model of Pulmonary Arterial Hypertension

Abstract

Chayil Gunpath*

Pulmonary arterial hypertension is a rare but a rapidly increasing prevalent pulmonary disease that is characterised by vasoconstriction and inflammation of the pulmonary arteries leading to elevated pressure in the system eventually causing right heart failure and death. Cannabidiol (CBD), which is the major non-psychoactive component of cannabis, has substantial anti-inflammatory, immunomodulatory, and analgesic effects. This study investigated the therapeutic potential of cannabidiol alone, and adjunctive therapy with selexipag, used in the treatment of PAH, by investigating its effects on the expression of the inflammatory and hypoxic biomarker, TNF-α, as well as the effect on BNP levels and oxidative stress in the blood and heart in a Monocrotaline (MCT)-induced PAH rat model. Forty male Sprague-Dawley rats were divided into 5 groups of 8 animals consisting of: Control, MCT-Control, MCT-CBD, MCT-selexipag, and MCT-CBD-selexipag groups. The study ran for a total of 36 days with MCT (60 mg/kg) being injected interperitoneally on day 0 to 4 groups to induce PAH, CBD (10 mg/kg), Selexipag and a CBDselexipag combination were administered daily by oral gavage from day 21 onward to their respective groups. Post experiment, gene expression in the heart for TNF-α, BNP in the plasma, and Total Antioxidant Capacity (TAOC) in the heart and plasma were determined, as well as a full haematological profile. Study results showed that both CBD and selexipag treatment increased the expression of BNP and decreased TAOC levels in the plasma most when co-administered. The highest TNF-α and T-AOC levels were recorded in the heart in the MCT-CBD group. Haemoglobin and platelet counts were also the highest in the MCT-CBD group. This shows us that CBD show’s promise as another therapeutic option in the treatment of PAH by targeting BNP, but only when taken in combination with selexipag. CBD also shows promise by decreasing oxidative stress, increasing T-AOC, in the heart during PAH. CBD did, however, not show promise in decreasing TNF-α levels, but rather increase it.