New insights into vascular reactivity: from altered structure to neural control

1. The present review covers two aspects of the author's research into the pharmacology of vascular reactivity of isolated vessels and in the intact circulation. First, how 'normal' reactivity is altered by injury or disease and, second, how novel drugs have allowed insight into the role of the cotransmitter neuropeptide Y and 'N' type calcium channels in neurotransmitter release. 2. Acute endothelium removal in the femoral artery of the anaesthetized dog confirmed the obligatory role of these cells in the dilatation response to intra-arterial acetylcholine (ACh). After 4 weeks, conduit arteries respond with a thickened neointima following acute endothelial injury but, provided macrophage-derived foam cells are absent, the artery relaxes normally to ACh. 3. In the dog coronary vasculature, stable collateral arteries have a marked neointima of non-contractile smooth muscle cells that are lined with endothelium. Reactivity to vasodilator stimuli is normal while that to vasoconstrictor stimuli is impaired. 4. In the conscious rabbit, superficial femoral artery (SFA) occlusion stimulates profound angiogenesis but, despite these changes to the hindlimb vasculature, reactivity to vasodilator and vasoconstrictor agents from day 1 to 6 months following SFA is unaltered. 5. Endothelial dysfunction is discussed in relation to hypertension, hypercholesterolaemia and congestive heart failure. 6. The novel "N' type calcium channel antagonist omega-conotoxin GVIA, was used to explore the role of "N' type channels in cardiac and vascular neurotransmitter release in conscious rabbits. 7. The novel putative Y 1-selective neuropeptide Y antagonist 1229U91 was shown to inhibit nerve-mediated contractions of isolated mesenteric, but not femoral, artery segments in the rat. This regional difference in a possible cotransmitter role of the peptide is discussed.