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D D Heistad

Publications and source records attributed to D D Heistad.

At least 73 records · Page 4Linked to original sources
PubMed1997

Mildly oxidized low-density lipoprotein impairs responses of carotid but not basilar artery in rabbits.

BACKGROUND AND PURPOSE: Intracranial blood vessels appear to be relatively resistant to development of atherosclerosis. The goal of this study was to compare effects of mildly oxidized LDL (ox-LDL) on endothelium-dependent responses of intracranial and extracranial arteries in vitro. METHODS: LDL was purified from plasma of healthy subjects and mildly oxidized by means of a xanthine/xanthine oxidase reaction. Contraction of the rabbit basilar and carotid arteries in response to histamine and phenylephrine and relaxation in precontracted vessels to acetylcholine and sodium nitroprusside were evaluated after 30 minutes of exposure to LDL or ox-LDL (100 micrograms/mL). RESULTS: Exposure to LDL had little or no effect on vascular responses. After exposure to ox-LDL, contraction to histamine and phenylephrine and relaxation to acetylcholine were impaired significantly in carotid (P < .05) but not in basilar artery. Relaxation to sodium nitroprusside was not significantly impaired by ox-LDL in the basilar artery. In the carotid artery, relaxation to sodium nitroprusside was significantly impaired by ox-LDL when the vessels were precontracted with phenylephrine but not histamine. Impairment of vascular responses by ox-LDL was prevented by addition of superoxide dismutase, catalase, or dimethylthiourea to the LDL solution before addition of xanthine/xanthine oxidase. CONCLUSIONS: Mildly ox-LDL impairs contraction and endothelium-dependent relaxation in the carotid but not in basilar artery. Thus, intracranial arteries may be relatively resistant to mildly ox-LDL.

Animals↗
PubMed1997

Mechanisms of bradykinin-induced cerebral vasodilatation in rats. Evidence that reactive oxygen species activate K+ channels.

BACKGROUND AND PURPOSE: Relatively little is know regarding mechanisms by which reactive oxygen species produce dilatation of cerebral arterioles. The goal of this study was to test the hypothesis that vasodilator responses of cerebral arterioles to bradykinin, which produces endogenous generation of reactive oxygen species, involve activation of calcium-dependent potassium channels. METHODS: We used a cranial window in anesthetized rats to examine effects of catalase (which degrades hydrogen peroxide) on responses to bradykinin. In addition, we examined effects of tetraethylammonium (TEA) and iberiotoxin, inhibitors of calcium-dependent potassium channels, on responses of cerebral arterioles to hydrogen peroxide, bradykinin, and papaverine. RESULTS: In cerebral arterioles (baseline diameter = 40 +/- 1 microns) (mean +/- SE), hydrogen peroxide (10 and 100 mumol/L) produced concentration-dependent dilatation. TEA (1 mmol/L), an inhibitor of calcium-dependent potassium channels, produced marked inhibition of vasodilatation in response to hydrogen peroxide. For example, 100 mumol/L hydrogen peroxide dilated arterioles by 13 +/- 2% in the absence and 4 +/- 1% (P < .05 versus control) in the presence of TEA. Bradykinin (10 nmol/L to 1 mumol/L) also produced concentration-dependent dilatation of cerebral arterioles that was inhibited completely by catalase (100 U/mL). TEA or iberiotoxin markedly inhibited vasodilatation in response to bradykinin. For example, 100 nmol/L bradykinin dilated arterioles by 21 +/- 3% in the absence and 2 +/- 2% (P < .05 vs control) in the presence of iberiotoxin (50 nmol/L). CONCLUSIONS: These findings suggest that dilatation of cerebral arterioles in the rat in response to hydrogen peroxide, or hydrogen peroxide produced endogenously in response to bradykinin, is mediated by activation of calcium-dependent potassium channels. Thus, activation of potassium channels may be a major mechanism of dilatation in response to reactive oxygen species in the cerebral microcirculation.

Animals↗
PubMed1997

Effect of subarachnoid hemorrhage on cerebral vasodilatation in response to activation of ATP-sensitive K+ channels in chronically hypertensive rats.

BACKGROUND AND PURPOSE: Cerebral vasodilatation in response to aprikalim, an opener of ATP-sensitive K+ channels, is selectively augmented after subarachnoid hemorrhage (SAH). Vasodilatation in response to activation of ATP-sensitive K+ channels, however, is impaired during chronic hypertension. Hypertension may contribute to a worse outcome after SAH, but the nature of the relationship between hypertension and SAH is uncertain. In the present study we examined responses of the basilar artery to aprikalim after SAH in normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). METHODS: In anesthetized WKY and SHRSP, we measured changes in diameter of the basilar artery in response to aprikalim and papaverine using a cranial window 2 days after injection of 0.3 mL saline or autologous blood into the cistema magna. RESULTS: Under control conditions, aprikalim (0.1 to 1 mumol/L) and papaverine (10 to 100 mumol/L) produced dilatation of the basilar artery. After SAH, responses to aprikalim were not significantly altered in WKY and were markedly increased in SHRSP compared with saline-injected control rats. In contrast, vasodilator responses to papaverine were not changed by SAH in either WKY or SHRSP, suggesting that augmented vasodilatation in response to aprikalim after SAH was selective. CONCLUSIONS: Responses of the basilar artery to aprikalim were greatly augmented in SHRSP after SAH. Because vasodilator responses to many stimuli are impaired after SAH and cerebral vasodilator responses to several stimuli are impaired by chronic hypertension, augmented responses to activation of K+ channels despite the presence of hypertension are unusual.

ATP-Binding Cassette Transporters↗
PubMed1997

Gene transfer to cerebral blood vessels after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Vasospasm remains a major cause of morbidity and mortality after aneurysmal subarachnoid hemorrhage. One step toward gene therapy to prevent spasm of cerebral vessels is to determine whether subarachnoid blood prevents transgene expression. METHODS: Vasospasm was induced in mongrel dogs using the double-hemorrhage intracranial-injection model. Diameter of the basilar artery was assessed by angiography, and profound vasospasm (> 50% decrease in diameter) was demonstrated at 4 and 7 days. Recombinant adenovirus expressing nuclear-targeted beta-galactosidase (reporter gene) under the control of the cytomegalovirus promoter was injected into the cisterna magna at the same time as (n = 9) or 2 days after (n = 4) injection of blood for induction of vasospasm. Brains were removed and examined histochemically for expression of nuclear beta-galactosidase. RESULTS: At 2 to 7 days, beta-galactosidase was expressed in leptomeninges over the brain stem, cortex, cerebral arteries, in small vessels in the cerebrum and brain stem, and in the ependymal lining of the ventricles. Transgene expression was observed in adventitia of blood vessels but not in vascular muscle or endothelium. Transgene expression was observed after simultaneous injection of virus and blood or when virus was injected 2 days after blood. CONCLUSIONS: The findings indicate that intracisternal injection of recombinant adenovirus can be used for gene transfer to cerebral blood vessels and overlying meninges, even in the presence of cisternal blood. We speculate that transfer of genes using recombinant viral vectors that encode for enzymes with vasodilator function to cerebral blood vessels and perivascular tissues may be useful for prevention or treatment of cerebral vasospasm after subarachnoid hemorrhage.

Animals↗
PubMed1997

Increase in TUNEL positive cells in aorta from diabetic rats.

TUNEL staining, which allows detection of fragmented DNA in situ, is commonly used as an indication of apoptosis. Recent studies suggest that apoptosis is increased in several pathophysiological conditions. In this study we examined the hypothesis that chronic diabetes is associated with an increase in TUNEL staining of the aorta. Diabetic rats were studied 4-5 months after injection of streptozotocin (50 mg/kg). Aorta of diabetic and control rats were examined for TUNEL staining, morphology by electron microscopy, and DNA contamination in RNA preparation by polymerase chain reaction (PCR). TUNEL staining of aortic sections showed a 6 fold increase of positive cells in the media of diabetic aorta (22 +/- 6%) (mean +/- SE) compared with aorta from age-matched controls (3.6 +/- 0.9%, p < 0.05). Electron microscopy demonstrated typical apoptotic cells and bodies in the media of aorta from diabetic but not control rats. DNA contamination was found in RNA prepared from diabetic aorta, which was detected using PCR, which is consistent with increased DNA fragmentation. Increased TUNEL staining was not observed in rats with hyperglycemia 3 days after injection of streptozotocin. In conclusion, severe chronic diabetes is associated with an increase in TUNEL staining, and perhaps apoptosis, in the aorta. We speculate that increased apoptosis may compensate for increased proliferative activity in diabetic blood vessels.

Animals↗
PubMed1997

Novel methods for adenovirus-mediated gene transfer to blood vessels in vivo.

Adenovirus-mediated gene transfer is a promising method for studies of vascular biology and potentially for gene therapy. Intravascular approaches for gene transfer to blood vessels in vivo generally require interruption of blood flow and have several limitations. We have used two alternative approaches for gene transfer to blood vessels in vivo using perivascular application of vectors. First, replication-deficient adenovirus expressing nuclear-targeted bacterial beta-galactosidase was injected into cerebrospinal fluid via the cisterna magna of rats. Leptomeningeal cells over the major arteries were efficiently transfected, and adventitial cells of large vessels and smooth muscle cells of small vessels were occasionally stained. When viral suspension was injected with the rat in a lateral position, the reporter gene was expressed extensively on the ipsilateral surface of the brain. Thus, adenovirus injected into cerebrospinal fluid provides gene transfer in vivo to cerebral blood vessels and, with greater efficiency, to perivascular tissue. Furthermore, positioning of the head may 'target' specific regions of the brain. Second, vascular gene delivery was accomplished by perivascular injection of virus in peripheral vessels. Injection of the adenoviral vector within the periarterial sheath of monkeys resulted in gene transfer to the vessel wall that was substantial in magnitude although limited to cells in the adventitia. Approximately 20% of adventitial cells expressed the transgene, with no gene transfer to cells in the intima or media. These approaches may provide alternative approaches for gene transfer to blood vessels, and may be useful for studies of vascular biology and perhaps vascular gene therapy.

Adenoviridae↗
PubMed1996

Vascular dysfunction in monkeys with diet-induced hyperhomocyst(e)inemia.

Elevated plasma homocyst(e)ine may predispose to complications of vascular disease. Homocysteine alters vasomotor regulatory and anticoagulant properties of cultured vascular endothelial cells, but little is known about effects of hyperhomocyst(e)inemia on vascular function in vivo. We tested the hypothesis that diet-induced moderate hyperhomocyst(e)inemia is associated with vascular dysfunction in cynomolgus monkeys. Plasma homocyst(e)ine increased from 4.O +/- O.2 microM when monkeys were fed normal diet to 10.6 +/- 2.6 microM when they were fed modified diet (mean +/- SE; P = 0.02). Vasomotor responses were assessed in vivo by quantitative angiography and Doppler measurement of blood flow velocity. In response to activation of platelets by intraarterial infusion of collagen, blood flow to the leg decreased by 42 +/- 9% in monkeys fed modified diet, compared with 14 +/- 11% in monkeys fed normal diet (P = 0.008), Responses of resistance vessels to the endothelium-dependent vasodilators acetylcholine and ADP were markedly impaired in hyperhomocyst(e)inemic monkeys, which suggests that increased vasoconstriction in response to collagen may be caused by decreased vasodilator responsiveness to platelet-generated ADP. Relaxation to acetylcholine and, to a lesser extent, nitroprusside, was impaired ex vivo in carotid arteries from monkeys fed modified diet. Thrombomodulin anticoagulant activity in aorta decreased by 34 +/- 15% in hyperhomocyst(e)inemic monkeys (P = 0.03). We conclude that diet-induced moderate hyperhomocyst(e)inemia is associated with altered vascular function.

Animals↗
PubMed1996

Effect of subarachnoid hemorrhage on dilatation of rat basilar artery in vivo.

Cerebral vasodilator responses are often impaired following subarachnoid hemorrhage (SAH). Because depolarization of vascular muscle may occur after SAH, we tested in vivo the hypothesis that SAH may augment dilatation in response to hyperpolarization due to activation of K+ channels. Anesthetized rats were studied two days after injection of saline or autologous blood into the cisterna magna. Diameter of the basilar artery in vivo was 224 +/- 5 microns (mean +/- SE) in saline-treated rats and 201 +/- 6 microns in SAH rats (P < 0.05). In control rats, acetylcholine (ACh), sodium nitroprusside (SNP), aprikalim and calcitonin gene-related peptide (CGRP; both activators of ATP-sensitive K+ channels), papaverine, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), and brain natriuretic peptide (BNP; an activator of particulate guanylate cyclase) produced concentration-dependent dilatation. In SAH rats, vasodilatation was impaired in response to ACh and SNP. In contrast, vasodilator responses to aprikalim and CGRP were augmented in SAH, rats (by two- to fourfold). Vasodilator responses to 8-BrcGMP, papaverine, and BNP were similar in both groups. Thus responses mediated by activation of soluble guanylate cyclase are selectively impaired by SAH, but responses to guanosine 3',5'-cyclic monophosphate are normal. Vasodilator responses to activation of ATP-sensitive K+ channels are augmented by SAH.

Adenosine Triphosphate↗
PubMed1996

Effects of endothelin receptor inhibition on cerebral arterioles in hypertensive rats.

The purpose of this study was to examine the effects of endothelin receptor inhibition on cerebral arterioles in stroke-prone spontaneously hypertensive rats (SHRSP). Structure and mechanics of cerebral arterioles were examined in untreated Wistar-Kyoto rats (WKY) and SHRSP that were either untreated or treated for 3 months with bosentan, an inhibitor of endothelin receptors (100 mg/kg per day). We measured pressure, external diameter, and cross-sectional area of the vessel wall (histologically) in maximally dilated (EDTA) arterioles on the cerebrum. Bosentan reduced but did not normalize arteriolar mean pressure (103 +/- 3 and 81 +/- 5 mm Hg in untreated and treated SHRSP versus 51 +/- 4 mm Hg in WKY, P < .05; mean +/- SEM) and pulse pressure (40 +/- 2 and 33 +/- 2 mm Hg in untreated and treated SHRSP versus 25 +/- 3 mm Hg in WKY, P < .05) in SHRSP. Cross-sectional area of the vessel wall (CSA) was increased in untreated SHRSP (1627 +/- 173 microm2), and CSA in treated SHRSP (1287 +/- 78 microm2) was similar to that in WKY (1299 +/- 65 microm2). Bosentan had no effect on reductions in external diameter (remodeling) of cerebral arterioles (104 +/- 7 and 96 +/- 4 microm in untreated and treated SHRSP compared with 126 +/- 7 microm in WKY, P < .05). Stress-strain curves indicate that bosentan had no significant effect on distensibility of arterioles on the cerebrum in SHRSP. The results suggest that endothelin-1 may contribute to the development of hypertrophy, but not remodeling or changes in distensibility, of cerebral arterioles in SHRSP.

Animals↗
PubMed1996

L-arginine restores dilator responses of the basilar artery to acetylcholine during chronic hypertension.

The objective of this study was to test the hypothesis that administration of L-arginine, a substrate for nitric oxide synthase, restores acetylcholine-induced dilatation of the basilar artery in chronically hypertensive rats. Basilar artery diameter was measured through a cranial window in anesthesized stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) aged 6 to 7 months (adult) and 12 months (older adult). Under control conditions, baseline basilar artery diameter was smaller in SHRSP (adult, 239 +/- 30 micron; older adult, 198 +/- 13 micron) (mean +/- SE) than in WKY (adult, 261 +/- 10 micron; older adult, 259 +/- 7 micron) (P <.05 versus SHRSP). Topical application of acetylcholine (10(-5) mol/L) produced dilatation of the basilar artery in WKY, which was impaired in both adult and older SHRSP (P <.05). Topical L-arginine (10(-3) mol/L for 30 minutes) did not affect responses to acetylcholine in adult SHRSP but enhanced vasodilatation in response to acetylcholine (10(-5) mol/L) in older SHRSP without affecting responses to sodium nitroprusside. In contrast, D-arginine did not affect acetylcholine-induced vasodilatation in older SHRSP. These results suggest that impaired dilatation of the basilar artery in response to acetylcholine in older SHRSP is restored toward normal by L-arginine, a substrate for nitric oxide synthase.

Acetylcholine↗
PubMed1996

Effect of short-term regression of atherosclerosis on reactivity of carotid and retinal arteries.

BACKGROUND AND PURPOSE: This study tested the hypothesis that functional abnormalities of carotid and ocular arteries may improve after short-term regression of atherosclerosis, before regression of structural abnormalities. METHODS: We examined effects of short-term dietary treatment of atherosclerosis on carotid and ocular vascular responses to serotonin and to platelet activation by collagen in vivo. Three groups of monkeys were studied: normal cynomolgus monkeys, monkeys fed an atherogenic diet for 34 months, and atherosclerotic monkeys that were fed a regression diet for 8.6 +/- 1.1 months (mean +/- SE). We measured changes in carotid blood flow (using a Doppler probe), retinal blood flow (using microspheres), and diameter of the internal carotid artery (using quantitative angiography). Endothelium-dependent relaxation to acetylcholine was studied in rings of internal carotid artery in vitro. RESULTS: Carotid blood flow increased in response to both serotonin and collagen in normal monkeys, decreased in response to both agents in atherosclerotic monkeys, and was restored toward normal after regression. Serotonin had little effect on retinal blood flow in normal monkeys and produced a marked decrease in retinal blood flow in atherosclerotic monkeys; the vasoconstrictor response to serotonin was reduced after regression. Activation of platelets by collagen increased blood flow in normal monkeys, decreased blood flow in atherosclerotic monkeys, and had little effect after regression. Alterations in responses of the internal carotid artery were consistent with changes in carotid and ocular blood flow. Endothelium-dependent relaxation in vitro was impaired by atherosclerosis and was restored toward normal by regression. There was no reduction in intimal area of the atherosclerotic lesion in common carotid and ophthalmic arteries from regression monkeys, despite a marked reduction in cholesteryl ester. CONCLUSIONS: Within a few months of regression of atherosclerosis, endothelial function and hyperresponsiveness of carotid and ocular arteries to serotonin and platelet activation return toward normal. Functional improvement is associated with resorption of lipid from atherosclerotic lesions, but with little reduction in size of intimal lesions.

Acetylcholine↗
PubMed1996

Role of Ca(2+)-dependent K+ channels in cerebral vasodilatation induced by increases in cyclic GMP and cyclic AMP in the rat.

BACKGROUND AND PURPOSE: The mechanisms by which cAMP and cGMP produce vasorelaxation are not entirely clear. In this study we examined the hypothesis that relaxation of cerebral arterioles in response to receptor-mediated activation of adenylate cyclase (increase in cAMP) is mediated through Ca(2+)-dependent K+ channels. METHODS: We measured the diameter of cerebral arterioles (basal diameter, 47 +/- 1 microns) using an open cranial window in anesthetized rats. Agonists and antagonists were applied locally in the cranial window. RESULTS: Topical application of adenosine (0.1 and 1 mmol/L), a receptor-mediated activator of adenylate cyclase, and dibutyryl cAMP (60 and 200 mumol/L), a cell-permeable analogue of cAMP, dilated cerebral arterioles. Iberiotoxin (50 nmol/L), a selective inhibitor of Ca(2+)-dependent K+ channels, reduced vasodilatation in response to 0.1 and 1 mmol/L adenosine by 66% and 28%, respectively. Tetraethylammonium (TEA) (1 mmol/L), another inhibitor of Ca(2+)-dependent K+ channels, reduced vasodilatation to 0.1 and 1 mmol/L adenosine by 58% and 42%, respectively, and reduced vasodilatation in response to 60 and 200 mumol/L dibutyryl cAMP by 75% and 66%, respectively. Topical application of sodium nitroprusside (0.1 and 1 mumol/L), a direct activator of guanylate cyclase, and 8-bromo cGMP (200 and 600 mumol/L), a cell-permeable analogue, produced dilatation of cerebral arterioles that was inhibited by iberiotoxin (50 nmol/L) and TEA (1 and 3 mmol/L). In contrast, dilatation of cerebral arterioles in response to papaverine (which produces vasodilatation in large part by inhibition of Ca2+ channels) and aprikalim (which produces vasodilation by activation of ATP-sensitive K+ channels) was not inhibited by iberiotoxin or TEA. CONCLUSIONS: These findings suggest that dilatation of cerebral arterioles by receptor-mediated activation of adenylate cyclase and by direct activation of guanylate cyclase in the rat is mediated in large part by activation of Ca(2+)-dependent K+ channels.

Adenosine↗
PubMed1996

Gene therapy for cerebral vascular disease.

BACKGROUND: Gene transfer to peripheral arteries has been accomplished with catheter-based approaches. Recently, gene transfer to the carotid artery and intracranial vessels has been achieved both in vitro and in vivo. Although gene therapy for cerebral vascular disease may not be accomplished for years, currently available methods probably will allow novel approaches to the study of vascular biology. PURPOSE: This mini-review summarizes current methodology and describes some potential goals of gene therapy. Transfection of vessels might be used to prevent vasospasm after subarachnoid hemorrhage, stimulate growth of collateral blood vessels, stabilize atherosclerotic plaques, and prevent restenosis after angioplasty. Gene transfer approaches also may be useful in treating ischemia by inhibition or overexpression of cytokines and by effects on neurons. Some formidable barriers to gene therapy are the current lack of safe and effective vectors for gene transfer, the difficulty in delivering vectors to intracranial vessels, and the transience of transfection. CONCLUSIONS: At present, gene transfer is a promising tool for the study of vascular biology. Obstacles to gene therapy for cerebral vascular disease seem sufficiently large that new approaches, rather than refinement of current approaches, may be needed. Progress toward gene therapy probably will be made in steps rather than leaps.

Animals↗
PubMed1996

Vascular expression of inducible nitric oxide synthase is associated with activation of Ca(++)-dependent K+ channels.

We tested the hypothesis that expression of inducible nitric oxide synthase (NO-synthase) in response to endotoxin (lipopolysaccharide) produces activation of potassium channels. Contraction of the rat thoracic aorta in response to phenylephrine was measured in vitro after treatment in vivo for 15 hr with vehicle (control) or lipopolysaccharide (10 mg/kg i.p.). Impaired contraction in response to phenylephrine was used as an index of inducible NO-synthase expression, and activation of potassium channels was examined with specific inhibitors. Contraction in response to 10(-5) M phenylephrine (expressed as a percentage of contraction in response to 85 mM KCI) was markedly impaired in lipopolysaccharide-treated rats, compared with control (15 +/- 5% vs. 131 +/- 10%, P < .05, mean +/- S.E.). Expression of inducible NO-synthase mRNA in the vessel wall in lipopolysaccharide-treated rats was confirmed using reverse transcription-polymerase chain reaction. Contraction of the aorta in lipopolysaccharide-treated rats was restored to normal by 0.3 mM aminoguanidine (an inhibitor of inducible NO-synthase). Contraction of the aorta in response to phenylephrine, which was inhibited by lipopolysaccharide, was not affected by glibenclamide (an inhibitor of ATP-sensitive potassium channels) but was increased 2-fold (P < .05) by iberiotoxin (50 nM), an inhibitor of Ca(+2)-dependent potassium channels. Relaxation of the aorta in response to sodium nitroprusside, an exogenous donor of nitric oxide, and 8-bromo-cyclic GMP was also inhibited by iberiotoxin. These findings suggest that nitric oxide produced by vascular expression of inducible NO-synthase activates calcium-dependent potassium channels and that this mechanism may contribute to impaired vasoconstrictor responses during sepsis.

Animals↗
PubMed1996

[The vasa vasorum of the arteries].

Nourishment of arteries is accomplished by diffusion from the lumen of the vessel and from vasa vasorum. Most normal arteries have an extensive network of vasa in the adventitia that arise from branch points of parent arteries. When the thickness of arteries exceeds the ability of simple diffusion of nutrients from the lumen (larger muscular of atherosclerotic arteries), vasa extend into the media and intima. Vasa in the intima-media arise predominantly from adventitial vasa, but can arise from the lumen in vascular grafts and recanalized arteries after thrombosis. Vasa respond to vasoactive stimuli, and can regress after they vascularize arterial grafts and in response to regression of the atherosclerotic lesions. Therefore, vasa can increase blood flow to the artery wall by dilation of existing arteries or by formation of new vessels (neovascularization). Conversely, vasa can reduce blood flow to the artery wall by active constriction or by regression (involution) of existing vasa. The pathophysiological significance of vasa vasorum in normal and diseased arteries is related to their structure. Vasa in the intima-media are thin-walled endothelial cell tubes with thin or absent medial smooth muscle cells. Therefore, they are prone to collapse and rupture in response to arterial pressure, mechanical forces in the artery, necrotic substances found in diseased arteries, and vasospasm. Vasa also provide the artery with a vast absorptive endothelial surface that may have important implications for arterial lipid kinetics, and delivery and removal of neurohumoral agents from the artery wall. These properties have lead to speculation about their role in the pathogenesis of atherosclerosis, plaque rupture and thrombosis, medial ischemia leading to arterial dissection and aneurysm, restenosis after angioplasty, and post-stenotic dilatation. Finally, larger veins also have an extensive network of vasa that have been implicated in the pathogenesis of venous thrombosis and varicose veins.

Aorta↗
PubMed1995

Evidence that angiotensin II is present in human monocytes.

BACKGROUND: The purpose of the present study was to determine whether human monocytes and polymorphonuclear leukocytes contain angiotensins I and II. METHODS AND RESULTS: Human mononuclear and polymorphonuclear leukocytes were isolated from blood. To identify angiotensins in human leukocytes, we performed immunocytochemistry using both alkaline phosphatase and fluorescence methods. With light microscopy immunocytochemistry with alkaline phosphatase, prominent staining of angiotensin II was observed in mononuclear leukocytes. Angiotensin I was also demonstrated in mononuclear leukocytes, but the signal was less pronounced than for angiotensin II. Polymorphonuclear leukocytes showed very little staining for angiotensin II. Fluorescence immunocytochemistry also demonstrated angiotensin II in mononuclear leukocytes. Angiotensins I and II in homogenate of leukocytes were quantified by radioimmunoassay. The concentration of angiotensins I and II in mononuclear leukocytes was 355 +/- 216 (mean +/- SEM) and 2331 +/- 106 fmol/mg protein, respectively, and the concentration in polymorphonuclear leukocytes was 36 +/- 10 and 336 +/- 120 fmol/mg protein. CONCLUSIONS: These findings suggest that human mononuclear leukocytes contain large amounts of angiotensin II and lesser amounts of angiotensin I. Human polymorphonuclear leukocytes contain small amounts of angiotensin I and II.

Adult↗