Blood vessels最新文献

The interaction between nitric oxide (NO) synthesized in one cell and cytosolic guanylate-cyclase-bound heme located in adjacent target cells to generate the NO-heme adduct of guanylate cyclase represents a novel and widespread signal transduction mechanism that links extracellular stimuli to the biosynthesis of cyclic GMP in target cells. A variety of chemical factors interact with selective extracellular receptors and trigger the biosynthesis of NO from L-arginine. The unique chemistry of NO endows this molecule with the capacity to diffuse rapidly into nearby cells and stimulate cyclic GMP formation. Cyclic GMP acts as a messenger in each cell type to trigger different but complementary cellular responses within a localized environment. This transcellular signaling is a form of rapid intercellular communication allowing the simultaneous local initiation of increased blood flow, inhibition of platelet-induced thrombosis and other cellular functions.

Activity of the efferent nerve supply to the vasculature results in local increases or decreases in the tone of the vascular smooth muscle cells with corresponding changes in diameter. This results in changes in pressure and flow, both of which, because they too influence the vascular wall, extend the influence potentially to the entire bed. As the vascular bed is sensitive to pressure - an increase causing vasoconstriction - and to flow - an increase causing variable amounts of contraction and relaxation - the final results must reflect their interaction. Thus, the direct changes in artery tone brought about by neural activity are modified and diffused throughout the entire regional arterial system by the concomitant changes in the flow and pressure of the blood.

Presynaptic serotonin (5-HT) receptors on the postganglionic sympathetic nerves, which mediate inhibition of noradrenaline release in blood vessels of various species and which interact with the presynaptic alpha 2-autoreceptors, are heterogeneous. In the rat vena cava, they are of the 5-HT1B subtype, in the pig coronary artery they belong to a novel, so far unknown class of 5-HT receptors, and in the human saphenous vein they could be classified as 5-HT1D. These results point to marked species differences and the need to carry out experiments in human vascular preparations. Presynaptic 5-HT receptors may be involved in the mechanism of action of the new antimigraine drug sumatriptan.

Heterogeneity represents a general feature of capillary networks. All of the parameters which describe hemodynamic, geometric or functional aspects of such networks exhibit considerable spatial dispersion. This is to some extent the result of the morphological and topological design of the network, reinforced by the nonhomogeneous nature of the flowing blood. Temporal dispersions are introduced by smooth muscle activity, which may be rhythmic or just oscillatory, but also by the passage of white cells causing transient perturbations. The functional relevance of perfusion heterogeneity follows from its effect on exchange efficiency. While evidence for the existence of physiological control mechanisms of heterogeneity is uncertain, intranetwork communication between upstream and downstream vessel segments appears to support the adaptation of supply to demand under physiological conditions.

Vasomotion is a potential target for drugs in vascular diseases. In this work, the effects on arteriolar vasomotion of norepinephrine, phentolamine and the vasoactive drug buflomedil were assessed in the hamster skinfold preparation. Results show the strong vasokinetic properties of alpha-sympathetic receptor activation by norepinephrine and an expected depressive effect of the alpha-blocker phentolamine. Buflomedil 10(-4) M enhances vasomotion and arteriolar reactivity and does not interfere with norepinephrine. The mechanism of these properties of buflomedil remains to be investigated.

Elucidation of the gene structure of several receptors known to mediate the signal of hormone or transmitter binding to intracellular effector systems through guanine-nucleotide-binding proteins (G proteins) has revealed that these receptors comprise a super-family of related proteins. The hallmark of all G-protein-linked receptors is a presumed topography of 7 membrane-spanning loops, analogous to the structure of bacteriorhodopsin. Members of this gene superfamily contain regions, particularly with the hydrophobic domains, of homologous sequence. The expression of G-protein-linked receptors in heterologous cell systems has allowed for the study of the pharmacological and biochemical properties of individual receptor subtypes in a manner not previously possible with intact tissues containing multiple receptors. Site-directed mutagenesis experiments have identified many conserved amino acids which are involved in ligand binding, receptor activation by agonists and receptor-G protein coupling, and suggest that the conservation of receptor structure throughout this gene family may reflect a conservation of important functional domains within these proteins.

In the rat vasculature, a single alpha 1-adrenoceptor may be coupled to two distinct G proteins, one of which regulates phospholipase C activity and is insensitive to pertussis toxin, and another which regulates calcium channel function and is highly sensitive to inhibition by pertussis toxin. alpha 1-Adrenoceptor agonists may in theory activate both pathways, but the efficiency of alpha 1-adrenoceptor coupling to the pertussis-toxin-insensitive pathway is low relative to the other pathway that couples the alpha 1-adrenoceptor to calcium channels. As such, only full agonists with high intrinsic efficacy can activate both pathways, whereas partial agonists, by virtue of their lower intrinsic efficacies, are less able to activate the pertussis-toxin-insensitive pathway, thereby rendering partial alpha 1-adrenoceptor agonists more sensitive than full alpha 1-adrenoceptor agonists to inhibition by calcium channel blockers and pertussis toxin.