Blood vessels最新文献

Ca2+ transients (1-2 microM) evoked by serotonin (5-HT) in cultured A7r5 cells were studied using fura-2 and digital imaging microscopy. Fura-2 was introduced into cells either by incubation with its acetoxymethyl ester analogue fura-2/AM or by transient ATP-induced permeabilization of the sarcolemma such that the free fura-2 entered the cell directly. The distribution of cytoplasmic Ca2+ in unstimulated cells loaded by the former method was heterogeneous, reflecting, in part, separate pools of Ca2+ in the cytosol and sarcoplasmic reticulum (SR). In contrast, the distribution of Ca2+ was uniform in cells loaded with fura-2 by transient permeabilization; this reflected the restriction of fura-2 to the cytosol. Average Ca2+ in these cells was substantially lower than that in fura-2/AM-loaded cells, because SR Ca2+ influences the fura-2 signal from fura-2/AM-loaded cells, but not from cells loaded with free fura-2. The differences in the Ca2+ distribution measured by the two loading methods were also evident during the course of 5-HT-evoked Ca2+ transients. Spatial and temporal resolution of the rising phase of 5-HT-evoked Ca2+ transients in fura-2/AM-loaded cells revealed that the onset of the Ca2+ transients was first manifested as small regions of elevated Ca2+ that subsequently expanded until peak apparent intracellular Ca2+ levels were present in virtually all of the nonnuclear regions of the cells. The rate of rise of Ca2+ varied in different cell regions with the nucleus responding the slowest.

Release of specific vasoactive peptides occurs upon activation of perivascular parasympathetic (vasoactive intestinal polypeptide and peptide histidine isoleucine), sympathetic (neuropeptide Y) and sensory (calcitonin gene-related peptide and tachykinins) nerves. These peptides may serve as cotransmitters with acetylcholine and noradrenaline with interactions both at the pre- and postjunctional levels. Some long-lasting nonadrenergic, noncholinergic vascular effects upon nerve activation may thus be peptide-mediated. Strong activation seems to be necessary for peptidergic transmission in the parasympathetic and sympathetic system while local sensory mechanisms may occur even at single impulses.

The influence of neuroeffector mechanisms in the regulation of postischemic cerebral blood flow was investigated by microsphere determination in 8 cats after chronic unilateral vascular deafferentation by trigeminal ganglionectomy. The animals were subjected to 90 min of reperfusion following 10 min of global ischemia induced by 4-vessel occlusion and systemic hypotension. Cortical hyperemia 30 min after reperfusion was attenuated by up to 48% in cortical gray matter ipsilateral to the side of trigeminal ganglionectomy (p less than 0.01). Axon reflex mechanisms involving the release of neuropeptides from peripheral sensory nerve fibers, such as substance P (SP), calcitonin gene-related peptide (CGRP) and neurokinin A (NKA), mediate this response. SP and NKA cause vasodilation by endothelium-dependent mechanisms (endothelium-dependent relaxing factor), whereas CGRP relaxes vascular smooth muscle by direct receptor interactions. Studies were therefore undertaken to determine the extent to which endothelium-dependent mechanisms mediate the hyperemia following global cerebral ischemia. In 7 intact cats, the postischemic response of pial arterioles to the topical application of acetylcholine (ACh; 10(-7) M), an endothelial-dependent vasodilator, was measured using a closed cranial window technique. Although ACh increased pial arteriolar caliber by 17% under resting conditions, the same dose elicited a vasoconstrictor response (87% of pre-ACh diameter 30 min after reperfusion) for the first 60 min of reperfusion after 10 min of ischemia. ACh-induced vasodilation was restored by 75 min (105%), but was less than control even at 120 min (109 vs. 117%; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Bioassay studies suggest that impaired endothelium-dependent relaxation in atherosclerotic arteries is due to a reduced release of biologically active endothelium-derived relaxing factor (EDRF). We tested the hypothesis that endothelial dysfunction is caused by deficiency of the EDRF precursor L-arginine. Aortae from normal and cholesterol-fed (1%, 4 months) rabbits were excised and incubated for 1 h with 5 mM L-arginine. Pretreatment with L-arginine had no effect on the relaxation to acetylcholine in normal vessels and was without effect on the impaired response of atherosclerotic arteries to acetylcholine. This finding suggests that L-arginine deficiency is unlikely the underlying cause of impaired endothelium-dependent relaxation in the aorta of cholesterol-fed rabbits.

Sudden occlusion of the middle cerebral artery (MCA) in normotensive rats increases blood flow through anastomosing branches into the territory of the occluded artery. Three weeks after MCA occlusion, anastomoses to anterior cerebral branches are increased by more than 50% in luminal diameter. One month after MCA occlusion, blood flow and blood flow reserve to the territory of the occluded MCA are returned to normal levels. In stroke-prone spontaneously hypertensive rats (SHRSP), the anastomoses are significantly narrower and blood flow through the anastomoses is less than in normotensive rats. Tissue infarction invariably develops in the territory of the occluded MCA in SHRSP. We propose that the luminal width of the anastomosis is a major determinant of blood flow into the territory of the occluded artery and of the amount of tissue protected from infarction by collateral circulation.

This paper reviews previous work done by my laboratory to investigate the effect of treatment with angiotensin-converting enzyme (ACE) inhibitors on blood pressure and small artery structure in spontaneously hypertensive rats (SHRs). First, the data confirm that ACE inhibitors have a persistent effect on blood pressure in SHRs when treatment is withdrawn. The effect of the ACE inhibitors was dose-dependent, but the persistent effect was not dose-dependent. This suggests that the persistent effect of ACE inhibitors on blood pressure in SHRs is not mediated through vascular structure. Secondly, the data demonstrate that, although ACE inhibitors have dose-dependent effects on both blood pressure and vascular structure, in experiments where different drugs were used, the effect of ACE inhibitors on vascular structure seems to be explained primarily through their effect on blood pressure, rather than any specific drugs effect.

Inhibition of angiotensin-converting enzyme (ACE) shifts the limits of cerebral blood flow autoregulation toward lower blood pressure values. This effect seems to be mediated by blocking the formation of angiotensin II on the luminal side of the larger cerebral resistance vessels. Baseline cerebral blood flow (the flow within the autoregulatory limits) is not changed by acute or chronic ACE inhibition. An interaction between the vascular reninangiotensin and the sympathetic nervous system is present. Activation of the latter inhibits the downwards shift of the upper limit of autoregulation following ACE inhibition.