Arterioles In Hypertension Research Articles

A mechanism for injury through cerebral arteriole inflation.

An increase in arterial pressure within the cerebral vasculature appears to coincide with ischemia and dysfunction of the neurovascular unit in some cases of traumatic brain injury. In this study, we examine a new mechanism of brain tissue damage that results from excessive cerebral arteriole pressurization. We begin by considering the morphological and material properties of normotensive and hypertensive arterioles and present a computational model that captures the interaction of neighboring pressurized arterioles and the surrounding brain tissue. Assuming an axonal strain-induced injury criterion, we find that the injury depends on vessel spacing, proximity to an unconfined free surface, and the relative difference in stiffness between the arterioles and the surrounding tissue. We find that a steeper heterogeneity (stiffer vessels surrounded by softer brain tissue) causes larger axial strains to develop at some distance from the arteriole wall, within the brain parenchyma. For a more gradual heterogeneity (softer vessels), we observe more larger strain fields close to the arteriole walls. Both deformation patterns are comparable to damage seen in previous pathology studies on postmortem TBI patients. Finally, we use an analytical model to approximate the interplay between internal pressure, arteriole thickness, and the variation in mechanical properties of arterioles.

Akt modulation by miR-145 during exercise-induced VSMC phenotypic switching in hypertension

AimsThis study investigated whether long-term exercise can influence vascular smooth muscle cells (VSMCs) phenotypic switching in mesenteric arteries of hypertensive rats, with a focus on the modulation of protein kinase B (PKB/Akt) signaling by microRNA-145 (miR-145). Main methodsIn the exercise intervention experiment, mesenteric arteries from 3-month-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were isolated for histological observation, phenotypic marker analysis, Akt phosphorylation quantification, and miR-145 evaluation after being subjected to moderate-intensity treadmill training (E) or being sedentary (C) for 8 weeks. In the transfection experiment, VSMCs were harvested to determine Akt phosphorylation and mRNA expressions of the upstream and downstream signaling molecules. Key findingsCalponin, a VSMC contractile marker, was significantly up-regulated in SHR-E relative to SHR-C (P < 0.05); while osteopontin (OPN), a dedifferentiation marker, was down-regulated in SHR-E relative to SHR-C (P < 0.05). Exercise significantly normalized the expression of miR-145 and significantly enhanced Akt phosphorylation (P < 0.05). In VSMCs over-expressing miR-145, Akt phosphorylation was significantly decreased (P < 0.05) with inhibited mRNA of both insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor substrate 1 (IRS-1). In VSMCs transfected with miR-145 inhibitor, Akt phosphorylation and mRNA of IGF-1R and IRS-1 were all down-regulated. miR-145 did not exhibit a clear effect on p70 ribosomal kinase (p70S6K), the downstream of Akt, following the transfections. SignificanceOverall, exercise remodels arterioles in hypertension and induces VSMCs maintaining contractile phenotype, in which miR-145 appears to be involved by inversely regulating Akt signaling via its upstream signals.

Mineralocorticoid exposure and receptor activity modulate microvascular endothelial function in African Americans with and without hypertension.

Prior work suggests blood pressure in African Americans is more sensitive to the effects of aldosterone than in Caucasians. This mechanism may relate to a negative response of the vascular endothelium to aldosterone, including reduced glucose-6-phosphate dehydrogenase (G6PD) activity. Thirty-three African Americans (11 hypertensives, 22 controls) without evidence of diabetes or metabolic syndrome completed the protocol. The protocol included measurement of in vivo microvascular endothelial function by digital pulse arterial tonometry and ex vivo measurement of endothelial function by videomicroscopy of arterioles obtained from these same subjects with and without exposure to aldosterone or spironolactone. Systemic and arteriolar G6PD activities were also measured. In vivo and ex vivo microvascular endothelial function were impaired in African Americans with hypertension. One-hour exposure with aldosterone impaired endothelium-dependent vasodilation in arterioles from normotensive subjects, while 1 hour of spironolactone exposure reversed endothelial dysfunction in arterioles from hypertensive subjects. G6PD activity was impaired in hypertensive arterioles. Aldosterone-related endothelial dysfunction may be responsible for at least a portion of the greater blood pressure sensitivity to aldosterone in African Americans. This may be in part related to vascular suppression of G6PD activity.

Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension

A morphometric study was performed on 22 renal biopsies from hypertensive patients with proteinuria and/or azotemia, with no evidence of other renal disease. These results were compared with our earlier study of normotensive aging kidneys. Afferent arterioles in hypertensive kidneys showed a significant increase in lumen diameter (15.7+/-4.9 vs 13.4+/-4.7 microm, P=0.0007) and wall area (1234+/-769 vs 998+/-445 microm(2), P=0.037), due primarily to shift in the distribution of arteriolar types, from predominantly normal toward predominantly hyaline arterioles in hypertension. Glomeruli were divided into four basic types: normal, hypertrophic, focal segmental glomerulosclerosis (FSGS) type, and sclerosing. Overall, glomeruli in hypertensive kidneys were much larger than in normotensive aging kidneys, for example, total capillary area (16 247+/-10 681 vs 11 624+/-5702 microm(2), P<0.00001). This increase was due primarily to an increase in size of each type, for example, for hypertrophic glomeruli: total capillary area (22 205+/-10 426 vs 15 349+/-4577 microm(2), P=0.0038). There was an excellent correlation between arteriolar lumen diameter and mean glomerular capillary area for hypertrophic/FSGS-type glomeruli (r=0.4778, P=0.0013), such that as arteriolar diameter increases the mean glomerular capillary area increases, consistent with loss of autoregulation. The morphologic correlates of loss of autoregulation, with afferent arteriolar dilatation and increase in glomerular capillary size, glomerular hypertrophy, and subsequent FSGS, are present on a focal basis in aging kidneys and, much more extensively, although still focally, in hypertensive kidneys.

Functional and structural involvement of afferent and efferent glomerular arterioles in hypertension

Functional and structural involvement of afferent and efferent glomerular arterioles in hypertension

The microcirculation in experimental hypertension and aging

The purpose of this manuscript is to review the literature concerning the alterations in the microvasculature in experimental hypertension and aging. We also present new unpublished data and results where previous studies have not addressed important questions. The new studies were performed using a chronic cranial window to allow multiple observations of the cortical surface vasculature over time. In vivo video, microscopic techniques were used to study long-term changes in microvascular caliber (vasomotion). In some studies, a chronic, in-dwelling aortic catheter allowed chaotic analysis of short-term blood pressure and heart rate variations. In these new studies we demonstrated a reduction in number of small arteriolar endpoints per cortical surface area in the spontaneously hypertensive rat and in the old Brown-Norway rat. There was also a reduction in the number of arteriole-to-arteriole anastomotic connections in the older rat. These vascular changes in the old rat were revised or prevented by caloric restriction. In the old rat, there was also a reduction in the variability of blood pressure, heart rate and microvessel caliber (vasomotion). These studies suggest that there is an alteration in the morphology of the small arterioles in hypertension and aging, that may lead to reduced ability to perfuse cortical tissue. In addition, there appears to be a diminution of overall short-term cardiovascular and microvascular control.

Distensibility and wall composition of rat cerebral arterioles in hypertension induced by chronic blockade of nitric oxide synthase

We have previously reported that, during chronic hypertension, cerebral arterioles undergo hypertrophy of the vessel wall, accompanied by a paradoxical increase in passive distensibility. We have proposed that this increase may be due to a reduction in the proportion of nondistensible (collagen and basement membrane) to the distensible (smooth muscle, elastin and endothelium) components of the vessel wall. We have recently observed in stroke-prone spontaneously hypertensive rats(SHRSP), that an endothelium derived factor, endothelin, may contribute to hypertrophy, but not to increases in passive ditensibility, of cerebral arterioles vessel wall.The goal of this study was to examine wall mass, composition and passive ditensibility of cerebral arterioles in chronic hypertension induced by decreased availability of another endothelium derived factor, nitric oxide (NO).Four weeks old male Sprague-Dawley rats were treated with LG-nitro-L-arginine methyl ester (LNAME; 10 mg /kg/day) in the drinking water. We examined distensibility of maximally dilated cerebral arterioles in 4 months old Sprague-Dawley rats. Arterioles were then fixed at physiological pressure (2.25% gluterladehyde in 0.10 mol/L cacodylate buffer), the arteriolar segment used for distensibility measurements was removed then immerse fixed, rinsed briefly in 0.1 M cacodylate buffer, osmicated and processed routinely for electron microscopy (TEM).

Effects of propranolol on intestinal microcirculation of normal and portal hypertensive rats

Background/Aims: The goal of the present study was to compare the efficacy of locally and systemically administered propranolol in normal and prehepatic portal hypertensive rats, and to test the hypothesis that β-adrenoceptor blockade reduces intestinal arteriolar diameter by allowing unopposed a-adrenergic activity. Methods: The small intestine was prepared for in vivo microcirculatory studies and transferred to an intravital microscope where arteriolar diameter and erythrocyte velocity were continuously monitored. First order arteriolar (1A) blood flow was calculated from the product of mean velocity and microvessel cross-sectional area. In separate experiments, diameter responses of 2A and 3A were monitored. Once steady-state conditions were achieved, the preparation was challenged by topically applied doses of propranolol (0.01–100.00 μM) in the presence and absence of the alpha-receptor antagonist, phentolamine. In a separate group of experiments, the effects of systematically administered propranolol (10 mg/kg body weight) were evaluated before and after local alpha-adrenoceptor blockade. Results: Propranolol produced significant vasoconstriction and decreased blood flow in both normal and portal hypertensive rats. Portal hypertensive arterioles exhibited an attenuated response to propranolol. Local administration of phentolamine completely blocked the propanolol-induced diameter changes. Comparison of equivalent concentrations of local and systemic propranolol indicated that both routes of administration were equally effective. Conclusion: The results of the present study suggest that the cardiovascular actions of propranolol are predominantly mediated through blockade of peripheral β 2-adrenoceptor.

Enhanced myogenic activation in skeletal muscle arterioles from spontaneously hypertensive rats

The purpose of this study was to determine whether the vascular myogenic response is enhanced in hypertension. Experiments were conducted in the intact cremaster muscle microcirculation as well as in isolated arterioles of hypertensive (SHR) and normotensive (WKY) rats. Increasing venous pressure in vivo by approximately 5 mmHg had no effect on normotensive first- (1A) or third-order arteriolar (3A) diameters; in contrast, hypertensive 1A diameter decreased 4% (89 +/- 2 to 85 +/- 3 microns) with an 8% decrease in 3A (24 +/- 2 to 22 +/- 2 microns). To further examine this enhanced constriction to elevated intravascular pressure in SHR, diameter was monitored in isolated 1A during step increases and decreases in intraluminal pressure. Normotensive arterioles displayed myogenic responses between pressures of 50 and 170 cmH2O; in contrast, hypertensive arterioles demonstrated myogenic responses over an extended pressure range (50-210 cmH2O). In addition, the change in diameter for each step change in pressure was greater in the arterioles from SHR, indicating an increased myogenic responsiveness. The myogenic reactions were unaffected by alpha-receptor blockade with phentolamine (10(-6) M), indicating that adrenergic hypersensitivity was not involved in the enhanced response to stretch. Morphometric analysis of the vascular wall revealed no differences in wall thickness, cross-sectional wall area, or wall-to-lumen ratio between normotensive and hypertensive rats. The length-tension relationships for normotensive and hypertensive rats demonstrated that peak active tension occurred at nearly the same vascular smooth muscle length. In addition, SHR arterioles were capable of maintaining higher levels of active tension that WKY arterioles, indicating an altered length-tension curve in chronic arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Heterogeneity of endothelial dysfunction in hypertension

The endothelium may play a role as a target and mediator of hypertension. Due to its anatomical position, it is very exposed to mechanical forces; as a source of vasoactive material it may participate in increasing peripheral vascular resistance and in promoting local ischaemia in the heart and brain. Morphological and functional changes in the endothelium occur in experimental and human hypertension. However, the severity of the defect and the mechanisms involved among vascular beds and models of hypertension are heterogeneous. Endothelium-dependent relaxations are impaired in the aorta, carotid artery and in cerebral and mesenteric arterioles in hypertension. In the coronary circulation the defect is less pronounced. The mechanisms involve a reduced formation of nitric oxide, an enhanced production of prostaglandin H2 and an impaired responsiveness of vascular smooth muscle to nitric oxide. The role of endothelin in hypertension is controversial; circulating levels appear unaltered except in the presence of renal failure or atherosclerosis. The local vascular production of endothelin, however, may still be increased. The potentiating effects of threshold concentrations of endothelin on the vasoconstrictor response to noradrenaline are enhanced in hypertension. Thus, subtle and distinct endothelial function defects occur in hypertension, but not all vascular beds are similarly affected and different mechanisms contribute. Endothelial dysfunction may contribute to increased peripheral resistance, tissue ischaemia and cardiovascular complications.

Calcium channel activation in arterioles from genetically hypertensive rats.

Enhanced contractile responsiveness to the calcium channel agonist Bay K 8644 has been documented in large conduit arteries and small muscular arteries from hypertensive rats. The present study examined the effects of Bay K 8644 on the intracellular calcium concentration ([Ca2+]i) in microvessels from stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. Using microspectrofluorometry of fura-2, [Ca2+]i was measured in smooth muscle cells localized on arteriolar fragments (15-35 microns external diameter) isolated after collagenase digestion of the pancreas. Resting [Ca2+]i in hypertensive arterioles (94 +/- 6 nM, n = 29) did not differ from that in normotensive vessels (81 +/- 4 nM, n = 40). KCl (50 mM), applied alone and in the presence of Bay K 8644 (30 nM), stimulated increases in [Ca2+]i that were reversed in calcium-free solution and with nifedipine (10 microM), consistent with activation of potential-operated calcium channels. Potassium-induced calcium transients were consistently potentiated by Bay K 8644. The change in [Ca2+]i evoked by KCl alone or in combination with Bay K 8644 did not differ between arterioles from hypertensive and normotensive rats. In 24% of the vessels from hypertensive rats and in 29% of those from normotensive rats, Bay K 8644 evoked an increase in [Ca2+]i that did not differ significantly between the two strains. The findings indicate that, in contrast to observations made in larger arteries, there is no evidence of a functional abnormality in potential-operated calcium channels in very small arterioles from genetically hypertensive rats.

Alterations in the microvasculature of one-kidney, one-clip hypertensive rats.

The microcirculation was studied in the cremaster muscle of one-kidney, one-clip (1K-1C) hypertensive rats and uninephrectomized controls under chloralose-urethan anesthesia 1-2, 4-5, or 8-9 wk following renal artery stenosis. With the use of television microscopy, inside and outside diameters of first (1A) through fourth-order (4A) arterioles were measured before and after vasodilation with 10(-4) M adenosine. Mean arterial blood pressure was significantly elevated in the 1K-1C rats, rising to 170 +/- 6 mmHg by 8-9 wks vs. 93 +/- 2 mmHg in controls. Enhanced vasoconstriction, resulting in closure of arterioles, appeared only in the smaller arterioles of 1K-1C and diminished throughout the development of hypertension. Structural rarefaction appeared later and increased with the development of hypertension. Vasodilated inside diameters of control, but not 1K-1C, 1A, 2A, and 3As, increased with increasing age, leaving the hypertensive arterioles with structurally reduced lumens and increased wall-to-lumen ratios, but without increases in wall cross-sectional areas. Structural lumen reduction appeared first in the 1A and advanced downstream as hypertension developed. Thus vasoconstriction of the smallest arterioles is important initially in renal hypertension, but structural alterations become more important later.

Pathology of small blood vessel disease in hypertension.

A pathogenic role for arterioles in hypertension has been postulated for many decades. Renal arteriolonecrosis, myointimal hyperplasia, and hyaline arteriolosclerosis are anatomic correlates of hypertension. The pathogenesis of these lesions is discussed as is contribution of these lesions to the perpetuation of hypertension. The importance of the extracellular matrix in the initiation and development of hyaline arteriolosclerosis is presented and correlated with the hemodynamic and pathophysiologic consequences of increased transmural pressure. The possibility of aiming therapy at arresting or ameliorating arteriolar disease is presented.

SEGMENTAL CALIBRE VARIATIONS IN SMALL ARTERIES AND ARTERIOLES IN HYPERTENSION - VASOSPASM OR VASODILATATION

Acta Neurologica ScandinavicaVolume 57, Issue s66 p. 54-60 SEGMENTAL CALIBRE VARIATIONS IN SMALL ARTERIES AND ARTERIOLES IN HYPERTENSION - VASOSPASM OR VASODILATATION First published: April 1978 https://doi.org/10.1111/j.1600-0404.1978.tb07637.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume57, Issues66April 1978Pages 54-60 RelatedInformation

An externally adjustable renal artery clamp.

ArticleAn externally adjustable renal artery clamp.C M Ferrario, C Blumle, G R Nadzam, and J W McCubbinC M Ferrario, C Blumle, G R Nadzam, and J W McCubbinPublished Online:01 Oct 1971https://doi.org/10.1152/jappl.1971.31.4.635MoreSectionsPDF (858 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByRenovascular Hypertension: Pathophysiology and Evaluation of Renal FunctionHemodynamic and reflex sympathetic control of transmural activation and rate of ventricular tachycardia in ischemic and hypertrophic ventricular myocardium of the dog.Circulation, Vol. 86, No. 2Effect of hypertension and hypertrophy on coronary microvascular pressure.Circulation Research, Vol. 71, No. 1Incidence of sudden cardiac death associated with coronary artery occlusion in dogs with hypertension and left ventricular hypertrophy is reduced by chronic beta-adrenergic blockade.Circulation, Vol. 82, No. 3Chronic hypertension and left ventricular hypertrophy facilitate induction of sustained ventricular tachycardia in dogs 3 hours after left circumflex coronary artery occlusionJournal of the American College of Cardiology, Vol. 14, No. 5Coronary angiogenesis during long-term hypertension and left ventricular hypertrophy in dogs.Circulation Research, Vol. 65, No. 2Acceleration of the wavefront of myocardial necrosis by chronic hypertension and left ventricular hypertrophy in dogs.Circulation Research, Vol. 63, No. 1Morphometry of canine coronary arteries, arterioles, and capillaries during hypertension and left ventricular hypertrophy.Circulation Research, Vol. 58, No. 1Effects of chronic hypertension and left ventricular hypertrophy on the incidence of sudden cardiac death after coronary artery occlusion in conscious dogs.Circulation, Vol. 65, No. 6Increased size of myocardial infarction in dogs with chronic hypertension and left ventricular hypertrophy.Circulation Research, Vol. 50, No. 1Effects of SQ 20,881 on the intact kidney of dogs with two-kidney, one clip hypertension.Hypertension, Vol. 2, No. 5Percutaneous Production of Renal Artery Lesions30 August 2016 | Acta Radiologica. Diagnosis, Vol. 20, No. 6Left ventricular mass and wall thickness in hypertensionThe American Journal of Cardiology, Vol. 44, No. 5Effect of renal hypertension and left ventricular hypertrophy on the coronary circulation in dogs.Circulation Research, Vol. 42, No. 4Characteristics of single carotid sinus baroreceptor fibers and whole nerve activity in the normotensive and the renal hypertensive dog.Circulation Research, Vol. 41, No. 6Renin, Aldosterone, Body Fluid Volumes, and the Baroreceptor Reflex in the Development and Reversal of Goldblatt Hypertension in Conscious DogsCirculation Research, Vol. 34, No. 4Abnormal endothelium-mediated regulation of coronary flow and arterioles in hypertension More from this issue > Volume 31Issue 4October 1971Pages 635-7 https://doi.org/10.1152/jappl.1971.31.4.635PubMed5111017History Published online 1 October 1971 Published in print 1 October 1971 Metrics

Calcium content of arteriolar walls in normotensive and hypertensive rats.

SummaryHypertension was produced in rats by narrowing one renal artery and removing the opposite kidney. These rats were then divided into 2 evenly matched groups. The rats in one of the groups were almost cured of hypertension; the rats in the other group remained hypertensive. The amount of calcium in the walls of the mesenteric arterioles was compared in the two groups. The hypertensive group, on the average, had 13% more arteriolar calcium than the “normotensive” group (P=0.01). Since calcium is known to promote the contraction of the muscle protein, actomyosin, the increased calcium content in the hypertensive arterioles may be partially responsible for their narrowed lumens.

Tissue cations and water in arterial hypertension.

Human hypertensive subjects were found to have an increased sodium and water concentration in renal artery and psoas muscle. Hypertensive rats showed a high water content in their aortas. If the water and sodium content were increased in hypertensive arterioles as well as arteries, the swelling of the arteriolar walls would narrow the lumens enough to account for much of the increased peripheral resistance. Low sodium diets may alleviate hypertension by lowering the sodium and water contents in arteriolar walls toward normal values.