Blood vessels最新文献

The mesenteric vasculature of Dahl salt-sensitive (DS) rats on high-salt diet is supersensitive to nerve stimulation and to norepinephrine. The current experiments were undertaken to examine whether the enhanced sensitivity to nerve stimulation is due solely to the postsynaptic supersensitivity to norepinephrine, to increased sympathetic innervation, to altered transmitter release or to the presence of another transmitter acting as a potentiator. Catecholamine content and neuropeptide Y (NPY) presence were determined in tissues from young (approximately 5 weeks old) male Dahl rats exposed to 5 days of high (7%) or low (0.45%) salt diet. Catecholamine content from mesenteric artery, renal artery, caudal artery, right atrium, aorta, vas deferens and adrenal gland was quantified by high-pressure liquid chromatography with an electrochemical detector. A strain difference, independent of diet, between young DS and Dahl salt-resistant (DR) rats was seen only in adrenal epinephrine content. DS high-salt (+) rats displayed reduced norepinephrine content relative to DR+ in the mesenteric artery and right atrium. The release of norepinephrine from isolated mesenteric vasculature into the perfusate in response to transmural stimulation showed no significant differences between DS+ and DR+ preparations under basal, or deoxycorticosterone acetate (DOCA; 30 microM) perfusion conditions. The addition of 5 microM cocaine to the DOCA perfusion, while increasing total norepinephrine outflow in all preparations, failed to differentiate between DS+ and DR+. NPY immunofluorescence along mesenteric artery sections of DS+ and DR+ rats was not significantly different. Thus, in the tissues examined, enhanced responsiveness of vascular smooth muscle may not be explained by hypernoradrenergic innervation, elevated NPY innervation or altered release of transmitter.

Two distinct peptides, C5a and f-Met-Leu-Phe (FMLP), that are chemotactic for phagocytic leukocytes affect profoundly the circulation in various in vivo systems. These peptides are known to relax strips of rabbit isolated blood vessels, the portal vein and pulmonary artery. In the present study, the effect of recombinant human C5a (2.5-25 nM) was examined and found to be qualitatively similar to that previously reported for FMLP. Indomethacin completely or partially inhibited the vasorelaxations induced by either peptide in the pulmonary artery and the portal vein, respectively. The relaxation induced by C5a was not abolished by removing the endothelial lining of the model vessels. The C5a or FMLP effects were more tachyphylactic in tissues continuously exposed to cycloheximide; this phenomenon was particularly pronounced for FMLP. A series of experiments were focused on the indomethacin-resistant component of the relaxation induced by either peptide on the portal vein. This component was not inhibited by capsaicin pretreatment or by endothelium removal, but was suppressed by treatment with NG-nitro-L-arginine or reduced by LY-83583. These findings suggest that the chemotactic peptides elicit their mechanical effect on rabbit vascular smooth muscle through the release of secondary mediators not related to the endothelium; the mediators are tentatively identified as prostaglandins and nitric oxide. It is the coordinated combinations of the metabolic pathways that are involved in the final responses, with inherent differences between vessel sources and the agonists used.

To evaluate whether intravascular phenomena contribute to local differences in growth responses of the arterial wall, we evaluated responses to organoid culture in a broad variety of arterial preparations. Arterial segments were isolated from adult, normotensive rats, sympathectomized, denuded from endothelium, and suspended in medium supplemented with serum. As judged from the nuclear incorporation of the thymidine analogue 5-bromo-2'-deoxyuridine (BrdUrd), this induced a transient stimulation of DNA synthesis in only a fraction of the arterial smooth muscle cells in all types of arteries. This intramedial DNA synthesis was more marked in renal arteries than in carotid arteries or aortae and was least pronounced in main pulmonary, femoral, and superior mesenteric artery and in mesenteric resistance-sized arteries. Organoid culture of isolated arteries did not increase the cross-sectional area of the media or the number of medial cells. It rather resulted in proliferation of smooth-muscle-like cells outside the media. In addition, smooth-muscle-like cells migrated out of the isolated arterial segments during culture. The rate of proliferation of these isolated cells did not differ between large arteries of different anatomical origin. However, isolated cells derived from mesenteric resistance arteries proliferated at a rate that was 4 times slower than that of large artery cells. The presence of endothelium significantly reduced medial DNA synthesis in carotid and renal artery segments, but not in mesenteric resistance-sized preparations. These data indicate that growth responses of the arterial wall differ quantitatively with the anatomical location and branching order of the vascular segment. In addition to the regional heterogeneity of endothelial effects on mitogenic responses of arterial smooth muscle, this seems to be due to regional differences in the susceptibility of arterial smooth muscle to exogenous growth factors. In this respect, we speculate that subsets of growth-resistant and growth-prone arterial smooth muscle cells could be heterogeneously distributed over the arterial tree.

We theorized that H-8, N-[2-(methylamino)ethyl]-5-isoquinolinesulfonamide, an inhibitor of cyclic nucleotide-dependent protein kinases, might be a useful probe to assess cyclic nucleotide-dependent relaxation of blood vessels. However, working in the rat caudal artery and aorta, we found that neither cyclic AMP- nor cyclic GMP-mediated relaxations were diminished by even large doses of H-8. For example, in the caudal artery, relaxation of a phenylephrine contraction by 8-bromo-cGMP (10(-5) M) was unaffected by H-8: control, 33 +/- 6.2%; 10 microM H-8, 41 +/- 12%; 30 microM H-8, 30 +/- 16% (p NS). The amount of relaxation by 8-bromo-cAMP (3 x 10(-4) M) was actually increased by H-8: control, 29 +/- 7.6%; 10 microM H-8, 34 +/- 7.4%; 30 microM H-8, 80 +/- 14%. In the rat aorta, H-8 also failed to diminish relaxation induced by 8-bromo-cGMP, or by atriopeptin II or sodium nitroprusside. In both caudal artery and aorta, H-8 of itself caused a dose-dependent suppression of alpha-adrenergic contraction: for example, in the caudal artery, with 10 or 30 microM H-8, peak contraction to phenylephrine was reduced to 70 (SEM) +/- 12% or 52 +/- 7% of control, respectively. The results suggest that the protein kinase inhibitor H-8 is not a useful probe to study cyclic nucleotide-dependent relaxation.

The endothelial cells help to control the tone of the underlying vascular smooth muscle by releasing vasoactive factors. In physiological circumstances, the release of relaxing factors (nitric oxide and endothelium-derived hyperpolarizing factor) appears to predominate. However, in certain blood vessels (peripheral veins and large cerebral arteries), the normal endothelium has the propensity to release vasoconstrictor substances, among which are superoxide anion and thromboxane A2; the release of these endothelium-derived vasoconstrictors may contribute to the autoregulatory processes. In most blood vessels, anoxic conditions initiate the release of an unidentified endothelium-dependent contracting factor. Cultured endothelial cells, and blood vessels maintained under culture conditions for prolonged periods of time, release the vasoconstrictor peptide endothelin. A characteristic of vascular diseases is that the ability of the endothelial cells to release relaxing factor(s) is reduced, while the generation of contracting factor is maintained or enhanced.

Graded stenoses (40-64% diameter reduction) were applied to dog common carotid arteries under anesthesia, and 27 days later the poststenotic velocity field was examined using transcutaneous pulsed Doppler velocimetry. Following in situ fixation, endothelial cell area, shape and orientation was measured by digitizing endothelial cell outlines in scanning electron micrographs. Endothelial cell area in the vicinity of the stenosis throat (within +/- 1 diameter) was reduced. No relation to stenosis hemodynamics was apparent. Cell area was increased 5 diameters downstream; in this region, there was turbulence due to jet break up. Cells were maximally rounded at the stenosis throat and gradually returned to upstream elongation by 5 diameters downstream. There was a region of flow separation and low velocity recirculation between the stenosis and the site of maximum turbulence, thus, downstream cell rounding was associated with flow separation. Subdivision of the experiments into four stenosis grades revealed little variation of the pattern of morphology between groups. It is possible that this is related to flow limitation with increasing grade. Elongation of endothelial cells through the entrance of the stenosis was apparent in only four experiments. Poststenotic dilatation of greater than 12% external diameter increase was noted in only four out of the sixteen experiments. In general, the relation of cell elongation to shear stress is supported, but this relationship does not fully explain endothelial cell shape at a stenosis.

In rat striated muscle, serotonin (5-hydroxytryptamine; 5-HT) constricts large arterioles (first-order; A1) via 5-HT2 receptor activation but dilates smaller arterioles via a 5-HT1-like receptor. In this preparation, A1 arterioles possess little basal tone. The purpose of this study was to determine if 5-HT would elicit A1 dilation if arteriolar tone was first induced. In anesthetized rats, A1 diameters of the cremaster muscle were measured via in vivo videomicroscopy. Topical application of angiotensin II caused a 26 +/- 3% constriction of the vessels. 5-HT dilated the preconstricted A1s by 36 +/- 7% while constricting normal tone A1s by 33 +/- 5%. This dilation was enhanced by blocking 5-HT2 receptors with LY53857, but abolished with methysergide, a 5-HT1 and 5-HT2 receptor antagonist indicating that the dilation was mediated by a 5-HT1-like receptor. Thus, A1 arterioles possess both 5-HT2 and 5-HT1-like receptors. The net result of 5-HT application in striated muscle, dilation or constriction, will depend on the initial tone of the vessels.

Vascular smooth muscle cells possess a number of Na cotransport systems. Three of these cotransport systems, Na/Ca exchange, Na/H exchange and Na-K-Cl cotransport, have been the subject of an increasing number of investigations to determine the respective roles of these transporters in vascular smooth muscle cell function. Evidence has been obtained that the Na/Ca exchange system participates in regulation of intracellular Ca in vascular smooth muscle cells. The Na/H exchange system appears to function in concert with a Cl/HCO3 exchange system to regulate intracellular pH. The Na-K-Cl cotransport system is a major contributor to K flux across the plasma membrane of vascular smooth muscle cells and is regulated by a number of vasoactive agents, suggesting that this Na cotransport system is also an important component of vascular smooth muscle cell function. Cultured vascular smooth muscle cells derived from spontaneously hypertensive rats have been found to exhibit reduced Na-K-Cl cotransport activity compared to smooth muscle cells from normotensive controls. Thus, alteration of vascular smooth muscle Na-K-Cl cotransport activity may be related to changes in vascular tone. However, the precise function of Na-K-Cl cotransport in vascular smooth muscle cells remains to be clarified. Recent studies of Na-K-Cl cotransport in vascular endothelial cells provide evidence that the co-transporter is important for regulation of endothelial cell volume and suggest that this Na cotransport system may be vitally important for normal function of the vasculature.

In intact smooth muscle, the calcium sensitivity of force may increase as well as decrease. Using differently skinned smooth muscle preparations, two pathways involved in the change of calcium sensitivity of force have been identified: in microarteries skinned with beta-escin, GTP (possibly via a G protein) is involved in sensitization to Ca2+, while in porcine coronary arteries skinned with Triton X-100 cyclic AMP and possibly cyclic GMP are involved in desensitization. In both cases, there is a corresponding change in the phosphorylation of the regulatory light chain of myosin, suggesting that the balance of phosphorylating to dephosphorylating reactions is altered at constant [Ca2+].