Given the cardiovascular effects of the cholinergic and cannabinoid systems, the present study aimed to investigate the interaction of both systems in hemorrhagic hypotensive conditions. Adult male Sprague Dawley albino rats were used in the study. Under sevoflurane anesthesia, the animals were catheterized in the left carotid arteries and jugular vein for monitoring cardiovascular parameters and producing hemorrhagic hypotension and intravenous (IV) injection, respectively. The hypotension was achieved by withdrawing a total volume of 2.2 mL blood/100g body weight over 10 minutes. The hemorrhage produced a severe and long-lasting decrease in mean arterial pressure (MAP). The IV injection of rimonabant (cannabinoid CB1 receptor antagonist) and DMSO promptly and significantly increased the MAP in the hypotensive rats. When administered at a sub-effective dose CDP-choline showed a slight increase in the MAP. However, when this same dose of CDP-choline was co-administered with DMSO, it elicited a more pronounced and prolonged increase in the MAP compared to the effects observed with CDP-choline or DMSO alone. Rimonabant partially inhibited the MAP-increasing effect of the sub-effective dose of CDP-choline administered with DMSO in the hypotensive rats. These findings suggest that CDP-choline demonstrates a synergistic interaction with DMSO, resulting in a heightened and prolonged increase in MAP during hemorrhagic hypotension. Conversely, it exhibits an antagonistic interaction with rimonabant in terms of their effects on MAP under similar conditions. These results can be interpreted as indicative of an interaction between cannabinoid CB1 receptors and the cholinergic system in the hemorrhagic hypotensive condition.
Yanar et al. (Mon,) studied this question.