Insight into the cardiovascular mechanisms of blood pressure lowering effect of gitogenin: a steroidal saponin

Background/objectives: Steroidal saponins are widely distributed in medicinal plants with potential applications in cardiovascular disorders. Gitogenin, a saponin, has not been explored as antihypertensive; this investigation was aimed to explore its blood pressure lowering potential and underlying mechanisms. Methodology: The effect of gitogenin was evaluated on blood pressure in vivo, using normotensive rat model and the underlying cardiovascular mechanism(s) in vitro, in isolated rat aorta and in atria preparations using PowerLab data acquisition system (ADInstrument, Australia). Results: Intravenous injection of gitogenin decreased mean arterial pressure (MAP) in anesthetized rats. Atropine (1 mg/kg) and L-NAME (100 mg/kg) pretreatment significantly (*p < .05) attenuated effect on MAP to gitogenin. In isolated intact aortic rings, gitogenin induced endothelium-dependent vasodilatation (maximum 65%), which was ablated (maximum 22%) with L-NAME (100 mg/kg) and atropine (1 mu M) pretreatment or endothelium removal. Gitogenin was found more potent against angiotensin II precontractions without effect on high K+ and low K+ precontractions. In isolated rat right atria, gitogenin suppressed rate and force of contractions. Atropine (1 mu M) pretreatment partially inhibited effect of gitogenin on force and eliminated its effect on rate. Combined atropine (10 mu M) and atenolol (0.5 mu M) pretreatment was without effect on force of contractions but eliminated effect of gitogenin on rate with 25% increase. Conclusion: These findings indicate that antihypertensive effect of gitogenin is the outcome of vascular and cardiac effects; agonistic effect on vascular M-3 and cardiac M-2 receptors; and being more selective for M-2. Increase in the rate of atrial contraction might be of clinical importance.

Automated summary

Gitogenin has the potential to lower blood pressure through its effects on vascular and cardiac mechanisms, with an agonistic effect on M-3 and M-2 receptors, being more selective for M-2. The increase in atrial contraction rate may be clinically important.