REVIEW Clonidine treats high blood pressure by stimulating a2 receptors in the brain, which decreases cardiac output and peripheral vascular resistance, lowering blood pressure. It has specificity towards the presynaptic a2 receptors in the vasomotor center in the brainstem. This binding decreases presynaptic calcium levels, and inhibits the release of norepinephrine (NE). The net effect is a decrease in sympathetic tone. It has also been proposed that the antihypertensive effect of clonidine is due to agonism on the I1-receptor (imidazoline receptor), which mediates the sympatho-inhibitory actions of imidazolines to lower blood pressure.
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