Blood vessels最新文献

Nonselective beta-adrenergic blockers have been reported to affect endothelium-dependent responses in isolated blood vessels in the following ways: (a) cause endothelium-augmented direct relaxations; (b) facilitate the endothelium-dependent relaxations evoked by alpha 2-adrenergic activation, or by acetylcholine; (c) augment the intraluminal release of vasodilator prostanoids, and (d) inhibit endothelium-dependent contractions to anoxia. Important species differences exist in terms of the endothelium-dependent effects of the compounds. If they were to occur in the intact organism, the endothelium-dependent effects of the beta-adrenergic blockers could help to explain their vasodilator properties.

The endothelins (ETs) are a family of newly discovered peptides with potent vasoconstrictor properties. They were first discovered in cultured endothelial cells but ET expression has since been found in many other tissues such as brain and kidney. They are peptides with 21 amino acids formed by hydrolytic cleavage of a larger peptide, big ET. Release of ETs from cultured endothelial cells is modulated by a variety of chemical and physical stimuli and as no storage sites have been identified it is suggested that endothelin release is regulated at the level of transcription or translation. Both big ET and ET-1 are found circulating in the blood. The levels are elevated in shock, myocardial infarction and kidney failure indicative of enhanced formation in these diseases. The literature now abounds with reports on actions of the ETs in vitro and in vivo. The vasoconstrictor properties are powerful and long-lasting. Several studies also show a mitogenic effect, indicating a possible trophic role. It is likely that in the next few years the development of inhibitors of endothelin synthesis and/or action will be of importance in unravelling the role of the ETs.

This paper is a review of the experimental evidence showing that specific binding sites for dihydropyridine Ca antagonists are involved in inhibition of stimulus-dependent Ca entry into arterial cells and thereby in inhibition of the contractile response. The apparent affinity of the dihydropyridine binding site is related to the proportion of a high- and a low-affinity state which is regulated by membrane potential but could also be dependent upon other factors such as G proteins. Among Ca antagonists, a subgroup of agents exhibiting voltage dependence may be identified. Their apparent pharmacological potency is highly dependent on resting membrane potential and on the duration of the depolarizing stimulus.

Mechanoreception, a widely distributed sensory modality, has been shown to be present in certain blood vessels. Changes in physical forces, like sudden increase of transmural pressure or flow velocity (shear stress), trigger changes in blood vessel diameter; the former reduces it while the latter increases vessel caliber. These changes in diameter, which are the result of contraction and relaxation of vascular smooth muscle in the blood vessel media, can serve the purpose of physiological regulation of blood flow (autoregulation) and protection of the intima against damages from high shear forces. The precise location of mechanosensor(s) and the mechanism of mechanoreception and signal transduction are poorly understood. Accumulating evidence suggests that the endothelium may be a site of mechanoreception and that changes in the synthesis/release of endothelium-derived relaxing (EDRF, EDHF, PGI2) and contracting factors (EDCF) result in altered vascular smooth muscle tone and vessel caliber. Increased shear stress stimulates the release of EDRF and PGI2 probably via activation of a K+ channel (inward rectifier) in endothelial cell membrane. Endothelium-dependent vascular contraction evoked by increased transmural pressure may be the result of (1) reduced release of EDRF (canine carotid artery) and (2) stimulation of the release of a still unidentified EDCF(s) (feline cerebral artery). Thus the endothelium can serve as pressure and flow sensor and is capable of transducing changes in mechanical forces into changes of vascular smooth muscle tone by modulating the release of endothelium-derived vasoactive factors. The physiological importance of the mechanoreception by endothelial cells in the intact circulation remains to be determined.

The amplification of alpha-adrenoceptor-mediated vasoconstriction by angiotensin II was studied in femoral artery rings from rabbits. Threshold concentrations of angiotensin II (0.1 nM) increased the maximal response to clonidine to 139 +/- 8% of control and produced a 3.2-fold increase in sensitivity. These effects of angiotensin II were reversed when tissues were pretreated with staurosporine (50 nM), an inhibitor of protein kinase C. The amplification of the alpha-adrenoceptor-mediated vasoconstrictor effects of thrombin and norepinephrine by angiotensin II were also reversed by pretreatment with staurosporine. Angiotensin II induced a response amplification in vascular smooth muscle known to be a nonspecific phenomenon, implying postreceptor interaction at intracellular transducer systems. Our findings suggest that upon activation of protein kinase C by angiotensin II, arterial responses to alpha-adrenoceptor agonists are amplified. This provides for nonspecific changes in vascular sensitivity by tonic alterations in postsynaptic modulation by enzyme systems known to regulate Ca2(+)-dependent phenomena, e.g. those related to vascular excitation-contraction mechanisms.