Regulation of vascular reactivity by established and emerging GPCRs

The vascular system is rich in G-protein-coupled receptors (GPCRs), particularly Class 1 GPCRs, which are activated by an eclectic range of chemical entities including peptides. These chemical messengers can function in blood vessels as directly acting vasoconstrictors, directly acting vasodilators or indirectly acting vasodilators. During the past ten years >50 receptors previously designated as 'orphan receptors' have been paired with their cognate ligands. New transmitter systems are emerging with some displaying potent activity in the vascular system, including the vasoconstrictors apelin, motilin, neuromedin U, sphingosine-1-phosphate and urotensin-II, and the vasodilators ghrelin and nociceptin. All Class 2 GPCRs are activated by peptides. Those displaying Vasoactivity all function as directly acting vasodilators and include adrenomedullin and the emerging urocortin transmitters. Hypertension can persist despite treatment with combinations of blood-pressure-lowering drugs. Thus, it is likely that further as yet undiscovered transmitter systems will provide new targets for novel therapies or diagnosis.