Changes In Caliber Of Vessels Research Articles

Acute Rho-kinase inhibition improves coronary dysfunction in vivo, in the early diabetic microcirculation

ObjectivesActivation of RhoA/Rho-kinase (ROCK) is increasingly implicated in acute vasospasm and chronic vasoconstriction in major organ systems. Therefore we aimed to ascertain whether an increase in ROCK activity plays a role in the deterioration of coronary vascular function in early stage diabetes.MethodsSynchrotron radiation microangiography was used to determine in vivo coronary responses in diabetic (3 weeks post streptozotocin 65 mg/kg ip) and vehicle treated male Sprague–Dawley rats (n = 8 and 6). Changes in vessel number and calibre during vasodilator stimulation before and after blockade of nitric oxide synthase and cyclooxygenase were compared between rats. Acute responses to ROCK inhibitor, fasudil (10 mg/kg iv) was evaluated. Further, perivascular and myocardial fibrosis, arterial intimal thickening were assessed by histology, and capillary density, nitrotyrosine and ROCK1/2 expressions were evaluated by immunohistochemical staining.ResultsDiabetic rats had significantly elevated plasma glucose (P < 0.001 vs control), but did not differ in fibrotic scores, media to lumen ratio, capillary density or baseline visible vessel number or calibre. Responses to acetylcholine and sodium nitroprusside stimulation were similar between groups. However, in comparison to control rats the diabetic rats showed more segmental constrictions during blockade, which were not completely alleviated by acetylcholine, but were alleviated by fasudil. Further, second order vessel branches in diabetic rats were significantly more dilated relative to baseline (37% vs 12% increase, P < 0.05) after fasudil treatment compared to control rats, while visible vessel number increased in both groups. ROCK2 expression was borderline greater in diabetic rat hearts (P < 0.053).ConclusionsWe found that ahead of the reported decline in coronary endothelial vasodilator function in diabetic rats there was moderate elevation in ROCK expression, more widespread segmental constriction when nitric oxide and prostacyclin production were inhibited and notably, increased calibre in second and third order small arteries-arterioles following ROCK inhibition. Based on nitrotyrosine staining oxidative stress was not significantly elevated in early diabetic rats. We conclude that tonic ROCK mediated vasoconstriction contributes to coronary vasomotor tone in early diabetes.

Retinal Arterioles Narrow with Increasing Duration of Anti-Retroviral Therapy in HIV Infection: A Novel Estimator of Vascular Risk in HIV?

ObjectivesHIV infection is associated with an increased risk of age-related morbidity mediated by immune dysfunction, atherosclerosis and inflammation. Changes in retinal vessel calibre may reflect cumulative structural damage arising from these mechanisms. The relationship of retinal vessel calibre with clinical and demographic characteristics was investigated in a population of HIV-infected individuals in South Africa.MethodsCase-control study of 491 adults ≥30 years, composed of 242 HIV-infected adults and 249 age- and gender-matched HIV-negative controls. Retinal vessel calibre was measured using computer-assisted techniques to determine mean arteriolar and venular diameters of each eye.ResultsThe median age was 40 years (IQR: 35–48 years). Among HIV-infected adults, 87.1% were receiving highly active antiretroviral therapy (HAART) (median duration, 58 months), their median CD4 count was 468 cells/µL, and 84.3% had undetectable plasma viral load. Unadjusted mean retinal arteriolar diameters were 163.67±17.69 µm in cases and 161.34±17.38 µm in controls (p = 0.15). Unadjusted mean venular diameters were 267.77±18.21 µm in cases and 270.81±18.98 µm in controls (p = 0.07). Age modified the effect of retinal arteriolar and venular diameters in relation to HIV status, with a tendency towards narrower retinal diameters in HIV cases but not in controls. Among cases, retinal arteriolar diameters narrowed with increasing duration of HAART, independently of age (167.83 µm <3 years of HAART vs. 158.89 µm >6 years, p-trend = 0.02), and with a HIV viral load >10,000 copies/mL while on HAART (p = 0.05). HIV-related venular changes were not detected.ConclusionsNarrowing of retinal arteriolar diameters is associated with HAART duration and viral load, and may reflect heightened inflammatory and pro-atherogenic states of the systemic vasculature. Measurement of retinal vascular calibre could be an innovative non-invasive method of estimating vascular risk in HIV-infected individuals.

Microvascular Dilatation after Haemodialysis Is Determined by the Volume of Fluid Removed and Fall in Mean Arterial Pressure

Background/Aims: The effects of haemodialysis on the microcirculation are poorly understood. This study examined the changes in small vessel calibre. Methods: 24 patients (including 12 males, median age 62.5 years, range 30–87) underwent digital retinal photography immediately before and after routine haemodialysis. Arteriolar and venular calibres were measured from the images by a trained grader using a highly reproducible, computer-assisted method. Results: Patients had an average 2.0 ± 0.3 litres of fluid removed with dialysis, and their mean arterial blood pressure fell by 6.8 mm Hg (CI 13.8–0.2, p = 0.06). Retinal arteriole calibre did not change (mean difference 2.3 µm, CI –1.1 to 5.7, p = 0.17) but the venules dilated (mean difference 12.7 µm, CI 7.3–18.3, p < 0.001). Calibre returned to baseline by 2 h. Venules dilated less in diabetics than non-diabetics (mean difference –6.2 µm, CI –9.6 to –2.9, p < 0.01). Retinal venular dilatation correlated positively with the volume of fluid removed per kilogramme body weight (5.9, CI 0.2–11.5, p = 0.04), and negatively with the fall in mean arterial pressure (–0.36, CI –0.72 to –0.01, p < 0.05) after adjusting for age, gender, diabetes and dyslipidaemia. Conclusion: Haemodialysis is associated with systemic venular dilatation.

Childhood Vascular Risk Factors and Retinal Vessel Caliber.

Variations in retinal vessel caliber have been associated with risk of ocular and systemic vascular diseases in adults. In this study, we examined the relationships between childhood vascular risk factors and retinal vessel caliber in young healthy adolescents. This was a cross-sectional study of 1225 adolescents recruited from 3 community-based schools in Singapore. Blood pressure and anthropometry measurements were obtained through standardized examinations. Birth weight was ascertained from health records completed by medical personnel soon after birth. Retinal vessel caliber was measured from retinal photographs using a semiautomated computer-based program following a validated standardized protocol. After adjusting for age, sex, and other relevant factors, each SD increase in blood pressure levels (systolic or diastolic) was associated with narrower arteriolar caliber (1.61 μm; P < 0.001); each SD increase in body mass index was associated with narrower arteriolar caliber (1.49 μm; P < 0.001) and wider venular caliber (2.68 μm; P < 0.001), and each SD decrease in birth weight was associated with narrower arteriolar caliber (1.31 μm; P = 0.001). Young adolescents with elevated blood pressure, obesity, or low birth weight have changes in retinal vessel caliber that are associated with ocular and systemic vascular diseases in adulthood. These findings provide evidence of possible adverse effects of childhood vascular risk factors on the retinal microvasculature early in life.

Screening for Retinal Vessel Caliber and Its Association with Metabolic Syndrome in Japanese Adults

Retinal microvasculature provides a direct means to assess microvascular health in vivo. We examined whether retinal vessel caliber is associated with the presence of metabolic syndrome in Japanese adults in a health screening program. We examined 1,003 Japanese adults through the health screening program conducted at the Shinoda General Hospital. Retinal vessel caliber was measured from digital fundus images using validated, semiautomated computer-assisted software. Metabolic syndrome was defined according to the definition proposed by the Joint Interim Statement in 2009. Cross-sectional associations between retinal vascular caliber and metabolic syndrome or its individual components were determined as odds ratios (ORs) using multiple logistic regression models. The overall prevalence of metabolic syndrome in the study sample was 29.9%. Persons with increased waist circumference and elevated triglycerides and blood pressure had significantly narrower retinal arterial diameters. Persons with increased waist circumference also had wider retinal venular diameters. Narrower retinal arterial diameters and wider retinal venular diameters were associated with a higher prevalence of metabolic syndrome (OR per -1 standard deviation (SD) change in arteriolar caliber=2.15, 95% confidence interval (CI) 1.45-3.18; OR per +1 SD change in venular caliber=1.53, 95% CI 1.04-2.26). We observed cross-sectional associations between retinal vessel caliber changes and metabolic syndrome and its components. We demonstrated that retinal vessel caliber assessments are feasible in health screening programs in a timely manner. Further longitudinal studies are warranted to determine whether retinal vessel caliber measurements can be used as noninvasive assessment to evaluate vascular health related to metabolic syndrome and cardiovascular diseases in health screening program.

Quantification of Pulsatile Changes in Retinal Vessel Caliber to Improve Non-Invasive Cardiovascular Risk Evaluation

Quantification of Pulsatile Changes in Retinal Vessel Caliber to Improve Non-Invasive Cardiovascular Risk Evaluation

Meta-analysis: Retinal Vessel Caliber and Risk for Coronary Heart Disease

Retinal vessel caliber may be a novel marker of coronary heart disease (CHD) risk. However, the sex-specific effect, magnitude of association, and effect independent of traditional CHD disease risk factors remain unclear. To determine the association between retinal vessel caliber and risk for CHD. Relevant studies in any language identified through MEDLINE (1950 to June 2009) and EMBASE (1950 to June 2009) databases. Studies were included if they examined a general population, measured retinal vessel caliber from retinal photographs, and documented CHD risk factors and incident CHD events. 6 population-based prospective cohort studies provided data for individual participant meta-analysis. Proportional hazards models, adjusted for traditional CHD risk factors, were constructed for retinal vessel caliber and incident CHD in women and men. Among 22,159 participants who were free of CHD and followed for 5 to 14 years, 2219 (10.0%) incident CHD events occurred. Retinal vessel caliber changes (wider venules and narrower arterioles) were each associated with an increased risk for CHD in women (pooled multivariable-adjusted hazard ratios, 1.16 [95% CI, 1.06 to 1.26] per 20-microm increase in venular caliber and 1.17 [CI, 1.07 to 1.28] per 20-microm decrease in arteriolar caliber) but not in men (1.02 [CI, 0.94 to 1.10] per 20-microm increase in venular caliber and 1.02 [CI, 0.95 to 1.10] per 20-microm decrease in arteriolar caliber). Women without hypertension or diabetes had higher hazard ratios. Error in the measurement of retinal vessel caliber and Framingham variables was not taken into account. Retinal vessel caliber changes were independently associated with an increased risk for CHD events in women.

Ultrafast High-Resolution In Vivo Volume-CTA of Mice Cerebral Vessels

Animal models developed in rats and mice have become indispensable in preclinical cerebrovascular research. Points of interest include the investigation of the vascular bed and the morphology and function of the arterial, capillary, and venous vessels. Because of their extremely small caliber, in vivo examination of these vessels is extremely difficult. In the present study we have developed a method to provide fast 3D in vivo analysis of cerebral murine vessels using volume computed tomography-angiography (vCTA). Using an industrial X-ray inspection system equipped with a multifocus cone beam X-ray source and a 12-bit direct digital flatbed detector, high-speed vCTA (180 degrees rotation in 40 s. at 30 fps) was performed in anesthetized mice. During the scan an iodinated contrast agent was infused via a tail vein. Images were reconstructed using a filtered backprojection algorithm. Image analysis was performed by maximum intensity projection (MIP) and 3D volume reconstruction. All mice tolerated i.v. injection of the iodinated contrast agent well. Smallest achievable voxel size of raw data while scanning the whole neurocranium was 16 mum. Anatomy of cerebral vessels was assessable in all animals, and anatomic differences between mouse strains could easily be detected. Mean vessel diameter was measured in C57BL/6 and BALBc mice. Changes of vessel caliber were assessable by repeated vCTA. Ultra fast in vivo vCTA of murine cerebral vasculature is feasible at resolutions down to 16 mum. The technique allows the assessment of vessel caliber changes in living mice, thus providing an interesting tool to monitor different features such as vasospasm or vessel patency.

Three-Dimensional Power Doppler Vascular Network Assessment of Adnexal Masses

The purpose of this study was to assess intraobserver and interobserver agreement for tumor vascular network evaluation as assessed by 3-dimensional (3D) power Doppler sonography for discriminating benign from malignant adnexal masses. Stored 3D power Doppler angiographic volume data from 39 women with a diagnosis of a vascularized adnexal mass who were evaluated and treated at our institution were retrieved from our database for analysis. Two different examiners (observer A, with 6 years of experience in 3D sonography; and observer B, with 1 year of experience) reviewed 3D sonograms blinded to each other. Three-dimensional vascular network reconstruction was done with surface rendering in the color mode. Malignancy was considered in the presence of at least 2 of the following: irregular branching, vessel caliber changes, microaneurysms, and vascular lakes. A definitive histologic diagnosis was obtained in all cases. Intraobserver and interobserver agreement rates were estimated by calculating the kappa index. Twenty (51%) tumors were malignant, and 19 (49%) were benign. Intraobserver agreement was good for observer A (kappa = 0.69) and moderate for observer B (kappa = 0.54). Interobserver agreement was moderate (kappa = 0.49). We found intraobserver and interobserver agreement to be moderate for 3D power Doppler assessment of the vascular network in adnexal masses.

Outflow boundary conditions for three-dimensional finite element modeling of blood flow and pressure in arteries

Flow and pressure waves emanate from the heart and travel through the major arteries where they are damped, dispersed and reflected due to changes in vessel caliber, tissue properties and branch points. As a consequence, solutions to the governing equations of blood flow in the large arteries are highly dependent on the outflow boundary conditions imposed to represent the vascular bed downstream of the modeled domain. The most common outflow boundary conditions for three-dimensional simulations of blood flow are prescribed constant pressure or traction and prescribed velocity profiles. However, in many simulations, the flow distribution and pressure field in the modeled domain are unknown and cannot be prescribed at the outflow boundaries. An alternative approach is to couple the solution at the outflow boundaries of the modeled domain with lumped parameter or one-dimensional models of the downstream domain. We previously described a new approach to prescribe outflow boundary conditions for simulations of blood flow based on the Dirichlet-to-Neumann and variational multiscale methods. This approach, termed the coupled multidomain method, was successfully applied to solve the non-linear one-dimensional equations of blood flow with a variety of models of the downstream domain. This paper describes the extension of this method to three-dimensional finite element modeling of blood flow and pressure in the major arteries. Outflow boundary conditions are derived for any downstream domain where an explicit relationship of pressure as a function of flow rate or velocities can be obtained at the coupling interface. We developed this method in the context of a stabilized, semi-discrete finite element method. Flow rate and pressure distributions are shown for different boundary conditions to illustrate the dramatic influence of alternative boundary conditions on these quantities.

Evaluation of arterial endothelial function using transit times of artificially induced pulses

Impairment of arterial endothelial function is an early event in atherosclerosis and correlates with the major risk factors for cardiovascular disease. The most widely employed non-invasive measure of endothelial function involves brachial artery (BA) diameter measurement using ultrasound imaging before and after several minutes of blood flow occlusion. The change in arterial diameter is a measure of flow-mediated vasorelaxation (FMVR). The high between-laboratory variability of results and cost of instrumentation render this technique unsuitable for routine clinical use. We induce artificial pulses at the superficial radial artery using a linear actuator. An ultrasonic Doppler stethoscope detects these pulses 10–30 cm proximal to the point of pulse induction. The delay between pulse application and detection provides the pulse transit time (PTT). By measuring PTT before and after 5 min of BA occlusion and ensuing reactive hyperemia, FMVR may be measured based on the changes in PTT caused by changes in vessel caliber, smooth muscle tone and wall thickness. We (1) validate the sensitivity of this technique to arterial wall tone using sublingual nitroglycerin and (2) compare measurements of endothelial function to ultrasound BA diameter measurements in 12 human subjects. The PTT-based method is verified to measure arterial wall tone and is shown to provide 37% greater sensitivity (p < 0.05) to FMVR than BA diameter measurements. By measuring the change in pulse transit time before and after endothelial stimulus, a sensitive, reproducible and convenient measure of endothelial function may be obtained at a low cost.

Changes in blood vessels in fetuses 4 to 9 months intrauterine life old by postmortem angiography method

We monitored changes in caliber, position and branching of blood vessels in fetuses of 4 - 9 months of intrauterine life. By precise dissection we prepared starting parts of common carotid artery and internal jugular vein in 40 cadaver fetuses. The vessels were injected with Telebrix and subjected to postmortem angiography at the Institute of Radiology Clinics Center in Sarajevo. Thereafter, arteries obtained were compared and analyzed. In preparations of few months old fetal material we observed arteries of fairly straight course, low caliber and with no observable ramification. When preparations of more mature stillborn infants were examined, we detected arteries of undulating course, more expressed ramification and higher caliber. In stillborn babies, all three arteries are of high caliber with rich branching. Considering that in this phase of brain development sulcuses are relatively wide, we can say that course of arteries is partially tortuous. Analysis of venous vessels shows good distinction of venous sinuses and subarachnoidal cisterns. We can conclude with great certainty that the changes occur in position, caliber and relationship among vessels in fetus during the period of brain sulci and gyri formation.

Retinal Vessel Diameters and the Incidence of Gross Proteinuria and Renal Insufficiency in People With Type 1 Diabetes

Early retinal vessel caliber changes may predict risk of diabetic nephropathy. We examined the association of retinal vessel diameters and the incidence of gross proteinuria and renal insufficiency in a population-based cohort of people with type 1 diabetes (n = 557). Baseline retinal photographs were digitized, and diameters of individual retinal vessels were measured and summarized. Incident cases of gross proteinuria and renal insufficiency were identified over a 16-year period. Larger retinal venular diameter was associated with higher cumulative incidence of gross proteinuria (18.6, 25.4, 37.7, and 50.4%, comparing increasing venular diameter quartiles) and renal insufficiency (10.7, 15.5, 23.2, and 32.8%). After adjusting for age, sex, duration of diabetes, HbA(1c) levels, baseline retinopathy levels, and other factors, larger retinal venular diameter was associated with an increased risk of gross proteinuria (RR 1.53, 95% CI 1.19-1.97, comparing 4th vs. 1st to 3rd quartiles of venular diameter) and renal insufficiency (1.51, 1.05-2.17). Retinal arteriolar diameter was not associated with either gross proteinuria or renal insufficiency. We conclude that in individuals with type 1 diabetes, larger retinal venular diameter is independently associated with the long-term incidence of gross proteinuria and renal insufficiency and may provide additional predictive information regarding risk of nephropathy.

Physiological and pathological role of the constitutively active α 1D adrenoceptors

In previous studies we have shown that in vessels where α 1D adrenoceptors have a functional role, this subtype exhibits constitutive activity, revealed by an increase in contractile tone, cytosolic calcium and inositol phosphate accumulation, in the absence of an agonist. The contraction and the two internal signals were inhibited by prazosin and BMY 7378, a selective α 1D adrenoceptor ligand. This constitutively active population of α 1D adrenoceptors plays a modulatory role in conductance vessels, preventing abrupt changes in vessel caliber, and consequently, in blood flow, when the stimulus disappears. The lack of this subtype in distributing arteries warrants a quick and fine adjustment of blood flow to adrenergic stimulus. An increased functionality of α 1D adrenoceptors in aorta, mesenteric and small mesenteric arteries of spontaneously hypertensive adult rats (SHR) has been observed. Consequently, the contractile tone of these vessels remained increased when the adrenergic stimulus disappears as compared with normotensive animals. This change is evidenced only when the hypertensive state appears as it is not observed in prehypertensive (young rats), or captopril-treated adult animals, therefore, it could be directly related to hypertension.

Magnetic resonance angiography in facial and other pain: neurovascular mechanisms of trigeminal sensation.

For much of the twentieth century migraine and cluster headache have been considered as vascular headaches whose pathophysiology was determined by changes in cranial vascular diameter. To examine nociceptive neural influences on the cranial circulation, the authors studied healthy volunteers' responses to injection of the pain-producing compound capsaicin in terms of the caliber of the internal carotid artery. The study was conducted using magnetic resonance angiographic techniques. Injection of capsaicin into the skin innervated by the ophthalmic (first) division of the trigeminal nerve elicited 40% +/- 27% (mean +/- SD) increase in vascular cross-sectional area in the right (ipsilateral) internal carotid artery when compared with the mean baseline ( P < 0.001). Injection of capsaicin into the skin of the chin to stimulate the mandibular (third) division of the trigeminal nerve and into the leg led to a similar pain perception and failed to produce any significant change in vessel caliber. The data suggest that there is a highly functionally organized, somatotopically congruent trigeminal innervation of the cranial vessels, with a potent vasodilator effect of the ophthalmic division on the large intracranial vessels. The data are consistent with the notion that pain drives changes in vessel caliber in migraine and cluster headache, not vice versa. These conditions therefore should be regarded as primary neurovascular headaches not as vascular headaches.

Expression of endothelial nitric oxide synthase after exposure to perivascular blood.

Although nitric oxide (NO) has been implicated in the development of vasospasm after subarachnoid hemorrhage, little is known regarding the time course of NO synthesis in vessel wall after exposure to perivascular blood. This study measures temporal characteristics of changes in vessel wall NO synthesis. Rat femoral arteries exposed to perivascular blood for 3, 5, or 7 days were assayed for the endothelial isoform of NO synthase (eNOS) by Western blot testing. Additionally, rat femoral arteries exposed to perivascular blood for intervals from 3 to 14 days were analyzed by means of immunohistochemistry for eNOS. Semiquantitative densitometry of femoral artery Western blots demonstrated a biphasic pattern of eNOS expression after exposure to perivascular blood. Compared with control arteries, eNOS expression increased at 3 days (53 +/- 36%), normalized at 5 days (-6 +/- 7%), and decreased by 7 days (-39 +/- 15%). Immunohistochemistry confirmed the changes in expression of immunoreactive eNOS in femoral endothelium during the first week after chronic perivascular blood exposure and apparent reduced eNOS immunostaining, which persisted up to 14 days after application of blood. The expression of endothelial-derived NO in rat femoral artery exposed to perivascular whole blood does not directly correlate with changes in vessel caliber during this interval. The biphasic expression of eNOS observed in these experiments highlights the complexity of processes occurring in the vicinity of the vessel wall during vasospasm and may be related to several mechanisms that modulate vessel tone and response to injury.

Expression of Endothelial Nitric Oxide Synthase after Exposure to Perivascular Blood

OBJECTIVE Although nitric oxide (NO) has been implicated in the development of vasospasm after subarachnoid hemorrhage, little is known regarding the time course of NO synthesis in vessel wall after exposure to perivascular blood. This study measures temporal characteristics of changes in vessel wall NO synthesis. METHODS Rat femoral arteries exposed to perivascular blood for 3, 5, or 7 days were assayed for the endothelial isoform of NO synthase (eNOS) by Western blot testing. Additionally, rat femoral arteries exposed to perivascular blood for intervals from 3 to 14 days were analyzed by means of immunohistochemistry for eNOS. RESULTS Semiquantitative densitometry of femoral artery Western blots demonstrated a biphasic pattern of eNOS expression after exposure to perivascular blood. Compared with control arteries, eNOS expression increased at 3 days (53 ± 36%), normalized at 5 days (−6 ± 7%), and decreased by 7 days (−39 ± 15%). Immunohistochemistry confirmed the changes in expression of immunoreactive eNOS in femoral endothelium during the first week after chronic perivascular blood exposure and apparent reduced eNOS immunostaining, which persisted up to 14 days after application of blood. CONCLUSION The expression of endothelial-derived NO in rat femoral artery exposed to perivascular whole blood does not directly correlate with changes in vessel caliber during this interval. The biphasic expression of eNOS observed in these experiments highlights the complexity of processes occurring in the vicinity of the vessel wall during vasospasm and may be related to several mechanisms that modulate vessel tone and response to injury.

Leukoencephalopathy with cerebral amyloid angiopathy: a semiquantitative and morphometric study.

To investigate changes in caliber of vessels in leukoencephalopathy with cerebral amyloid angiopathy (CAA) we performed a histological and morphometric study of cerebral arteries in this disease. We histologically examined changes in cortico-leptomeningeal arteries in five cases of leukoencephalopathy with CAA and compared their morphometrically determined wall-to-lumen ratio [(external diameter-internal diameter) x 0.5/internal diameter] with those of amyloid-negative arteries to estimate stenotic changes. Additionally, we compared wall-to-lumen ratios of medullary arteries in brains with CAA and white matter lesions (WML) (CAA(+)/WML(+), n = 5), subcortical arteriosclerotic encephalopathy without CAA (CAA(-)/WML(+), n = 7), and neither CAA nor white matter lesions (CAA(-)/WML(-), n = 5). Amyloid-positive arteries had thinned walls and dilated lumens. The external diameter and the wall-to-lumen ratio for amyloid-positive arteries was smaller than for amyloid-negative arteries in CAA(+)/WML(+) brains. There was no significant difference in the external diameters among the three groups. The wall-to-lumen ratio for medullary arteries in CAA(-)/WML(+) brains was significantly greater than for CAA(+)/WML(+) and CAA(-)/WML(-), but there was no significant difference between CAA(+)/WML(+) and CAA(-)/WML(-). Amyloid deposition causes degeneration of the tunica media, resulting in thinning of the wall and dilation of the lumen. The tunica media of small arteries is important in regulation of cerebral blood flow with degeneration causing impairment of cerebrovascular autoregulation in response to blood pressure. This impairment may lead to white matter lesions.

Pharmacologic Treatment of Migraine

The vascular theory of migraine proposed by Wolff, attributing migrainous symptoms to paroxysmal constriction and dilation of the cranial vasculature, held sway for over four decades and even now remains embraced by many clinicians and the lay public. Recent investigations, however, suggest that this proposed mechanism is untenable; although changes in blood vessel caliber and blood flow do occur in some patients during some attacks, they are not required for the production of migrainous symptoms and appear to be largely epiphenomena, occurring subsequent (and consequent) to another primary process. Evidence is mounting that migraine may result from a pathologic alteration of neurotransmission within the brain stem and trigeminovascular system, and one of the neurotransmitters primarily involved is serotonin. This has led to an explosion of interest in therapeutic agents which influence serotoninergic receptors, and the astounding success enjoyed by the first of these agents to be utilized clinically (sumatriptan and dihydroergotamine) and their offspring suggests that our understanding of this common and vexing problem will increase and be paralleled by the identification of yet more specific and effective treatment intervention.

Role of NO in flow-induced remodeling of the rabbit common carotid artery.

Flow-induced changes in vessel caliber tend to restore baseline wall shear stress (WSS) and have been reported to be endothelium-dependent. To investigate the role of endothelium-derived nitric oxide (NO) in the adaptive increase in artery diameter in response to a chronic increase in blood flow, an arteriovenous fistula was constructed between the left common carotid artery (CCA) and the external jugular vein in 22 New Zealand White rabbits, and NO synthesis was inhibited in 14 animals by long-term administration of NG-nitro-L-arginine-methyl ester (L-NAME) in drinking water given for 4 weeks. The remaining 8 animals served as controls. Mean arterial blood pressure was not significantly altered by L-NAME treatment (91 +/- 2 in control versus 98 +/- 3 mm Hg in L-NAME-treated rabbits). Blood flow significantly increased in the left CCA in both groups but was lower in L-NAME-treated than control animals (106.1 +/- 10.7 versus 196.2 +/- 32.3 mL/min, P < .003). The diameter of the flow-loaded left CCA also increased significantly in both groups compared with the right CCA (2.15 +/- 0.12 and 2.54 +/- 0.1 mm, respectively, P < .02), but the increase was less in the L-NAME-treated than the control group (3.24 +/- 0.09 and 4.64 +/- 0.17 mm, respectively, P < .0001). The diameter of the anastomosed veins was also increased but to a much lesser degree in L-NAME-treated animals than in controls (4.14 +/- 0.29 versus 7.94 +/- 0.51 mm, P < .0001). As a result of artery enlargement, WSS was normalized in the flow-loaded left CCA of the control group (8.87 +/- 0.77 dynes/cm2) regardless of blood flow values. In L-NAME-treated animals, however, WSS was only partially regulated, the mean value being significantly increased (18.7 +/- 2.2 dynes/cm2, P < .006). Moreover, a highly significant positive correlation between WSS and blood flow was obtained in L-NAME-treated animals (r = .84, P < .0001). We also found remodeling of the artery wall, with a larger increase in the medial cross-sectional area associated with an increased number of smooth muscle cells, in the control group compared with the L-NAME-treated group (0.75 +/- 0.09 versus 0.49 +/- 0.04 mm2 and 4504 +/- 722 versus 2717 +/- 282 cells/mm2, P < .03). We conclude that NO plays a role in the increase of vessel caliber in response to chronic increase in blood flow. As yet unidentified additional metabolic processes appear to be necessary for a complete regulatory response.