Small-diameter Arteries Research Articles

Smooth muscle hypertrophy and arterial remodelling in deoxycorticosterone acetate-salt hypertension.

Morphometric analyses were made of medial-intimal cross-sectional area and lumen diameter in transverse sections of large arteries and small arterioles from normal and deoxycorticosterone acetate-salt hypertensive animals whose vasculatures were perfusion fixed at their in vivo mean arterial pressures. During the borderline and established phases of hypertension, changes in medial cross sectional area and lumen diameter were not detected in any vessel. During chronic mineralocorticoid hypertension, significant (p < 0.05) medial hypertrophy and an increased lumen diameter were found in the abdominal aorta whereas these parameters were normal in other large conduits, small arteries, and arterioles examined. These results indicate that medial hypertrophy is a late consequence of chronic hypertension in this model and is confined primarily to the abdominal aorta. Further, remodelling without medial hypertrophy may explain the normal lumen diameters of small arteries and arterioles in this model of hypertension.

Interaction of myogenic and adrenergic mechanisms in isolated, pressurized uterine radial arteries from late-pregnant and nonpregnant rats

The purpose of this study was to examine how myogenic and adrenergic mechanisms interact in controlling the lumen diameter of small uterine arteries from nonpregnant and late-pregnant rats. Radial arteries (150 to 250 microns lumen diameter) from nonpregnant (n = 28) and late-pregnant (n = 18) rats were studied in vitro under conditions of varying transmural pressure and agonist concentrations. (1) Arteries from late-pregnant rats were significantly (p < 0.05) larger in diameter and, unlike nonpregnant vessels, developed a stable intrinsic tone at transmural pressures > 25 mm Hg. (2) Vessels from late-pregnant rats displayed a threefold increase in sensitivity to the constrictor effects of phenylephrine: 50% of maximal constriction, nonpregnant = 691 +/- 148 nmol/L and late-pregnant = 229 +/- 32 nmol/L (p < 0.01). (3) There was no difference in sensitivity to potassium depolarization. (4) Arteries from late-pregnant rats actively constricted to changes in transmural pressure, whereas those from nonpregnant did not unless preactivated beforehand with phenylephrine or K+. (5) After preconstriction the autoregulatory effectiveness of late-pregnant arteries in physiologic saline solution versus phenylephrine or K+, or of nonpregnant in K+ and phenylephrine, appeared to be equal in terms of absolute micrometers but not relative percent change in lumen diameter. Pregnancy is associated with significant changes in the active contractile properties of uterine resistance artery function, specifically heightened alpha-adrenergic sensitivity, intrinsic (pressure-dependent) tone, and myogenic reactivity.

A model for blood flow through a stenotic tube

This article deals with the introduction of the modified Casson's fluid model as the true representation for the blood for the steady laminar flow through a small diameter artery with axi-symmetric identical double stenoses in series. The governing equations are solved by using the finite element method. The results for the velocity profiles, the pressure and the wall shear stress distributions in addition to the location and length of the flow reversal zones have been brought out and discussed in reference to the severity of the disease. It has been observed that the non-Newtonian nature of the blood helps in reducing the magnitude of the peak wall shear stress at the throat and the length of the reversed flow regions in the post stenotic dilatation.

Selective and tone-dependent vasodilation of arterial segment in rabbit and feline pulmonary microcirculation in response to ANP.

Using an X-ray television system, we directly measured the changes in internal diameter (ID; 100-600 microns) of small pulmonary arteries and veins in response to intravenous infusion of atrial natriuretic peptide (ANP) in anesthetized rabbits and cats. Under physiological conditions, ANP (0.01-1 micrograms/(kg.min) for 3 min) increased the ID of the small arteries in a dose-dependent manner by 4-9% and by 6-14% in the rabbit and cat, respectively. The maximum increase in ID occurred in the 400-600 microns arteries. In the small veins, however, the peptide had no significant effects on the ID. To simultaneously investigate the ANP-induced responses of pulmonary vessels with different vascular tone in a given lung region, we embolized a part of the rabbit pulmonary vascular tree with micro-beads (80-100 microns diameter) and measured ID responses to ANP (1 microgram/(kg.min) for 3 min) in the embolized vessels with elevated tone and the nonembolized vessels with baseline tone. In the embolized arteries, which had constricted by 31%, ANP induced 27% increase in ID, while in the nonembolized arteries it caused 8% increase in ID. This indicated that in the small arteries, the vasodilator activity of ANP is greatly enhanced under the conditions of elevated vascular tone. In the small veins, however, no significant vasodilation occurred even under the elevated-tone conditions. We concluded that ANP dilates the arterial segments in the rabbit and cat pulmonary microcirculation selectively and in a dose-dependent manner. Furthermore, the pulmonary vasodilator effect of ANP was dependent on the pulmonary vascular tone.

Etiology, pathophysiology, and treatment of left ventricular hypertrophy: focus on severe hypertension.

Left ventricular hypertrophy (LVH), a common finding in hypertensive patients, has emerged as one of the most potent risk factors for future cardiovascular mortality in patients with hypertension. LVH is associated with multiple physiologic abnormalities, which may account for the increased risk. These include coronary perfusion abnormalities such as reduced coronary flow reserve, altered coronary flow autoregulation, subendocardial hypoperfusion, and abnormal left ventricular (LV) diastolic function. Although abnormalities of LV diastolic function are more common in LVH, they may occur early in the course of the disease. There may be a threshold of average awake ambulatory blood pressure (BP), 130/85 mm Hg, below which neither diastolic abnormalities nor LVH is detected. The reasons for reduced reserve coronary flow reserve are complex and include structural and functional abnormalities of myocardial blood vessels such as reduced capillary density, reduced luminal diameter of intramyocardial small arteries, and increased vascular tone, possibly as a result of factors such as abnormal endothelium-dependent relaxation. Preliminary data suggest that regression of LVH is associated with improved survival. Severe hypertensive patients would be expected to achieve the greatest benefit, because, if left untreated, this group has nearly 20% mortality within 2 years. To evaluate the effect of nifedipine gastrointestinal therapeutic system (GITS) on LV mass, 16 patients with initial diastolic BP > 120 mm Hg were treated for 1 year with either monotherapy or in combination with a thiazide diuretic. Because it has not been unequivocally shown that changes in LV mass have physiologic benefit, associated alterations in LV systolic function, LV filling, plasma renin activity, atrial natriuretic peptide, and catecholamines were also evaluated.(ABSTRACT TRUNCATED AT 250 WORDS)

Magnetic resonance imaging of small arteries

Magnetic resonance imaging (MRI) with receive-only surface coil technology was used to visualize and quantitate luminal diameters of small arteries in the rat. MRI measurements of normal and aneurysmal aortas, over a diameter range of 1–3 mm, were closely correlated with direct measurements made visually at laparotomy: measured differences averaged 0.16 mm, and the least-squares regression line ( R 2 = 0.97, P < 0.001) compared favorably to the line of equivalence, X = Y. This noninvasive but precise imaging modality demonstrates the potential value of using MRI to evaluate the diameter of small vessels, including the postoperative monitoring of arterial bypass graft patency in peripheral regions.

Skin arteriolar responses to local temperature changes in hypertensive rats.

A rat skin preparation was developed to determine if the responses of the resistance vessels to local skin warming and cooling were abnormal in spontaneously hypertensive rats (SHR). A major advantage of this preparation is that all the skin resistance vessels from small arteries preceding the microcirculation to small arterioles can be studied by intravital microscopy techniques. An abdominal skin flap was reflected with intact vasculature and positioned on a temperature-controlled manifold. Diameters of small arteries and large through small arterioles were measured at normal skin temperature (35 degrees C) and after cooling to 25 degrees C and warming to 38 degrees C, there were no differences in control diameters for comparable branching orders between normotensive (Wistar-Kyoto) and hypertensive rats; however, the maximum diameter of small arteries was 13% smaller in hypertensive rats. All arteriolar branching orders possessed vascular tone that was not altered by neural blockade with tetrodotoxin. With cooling to 25 degrees C, all branching orders constricted (range, 12-37%). The largest and smallest vessels of hypertensive rats constricted almost twice as much as their normotensive counterparts. With warming to 38 degrees C, only the smallest arterioles dilated (19% in normotensive versus 43% in hypertensive rats). This study demonstrates major differences in the arteriolar branching orders that respond to local warming and cooling of nonapical skin regions in both normotensive and hypertensive rats and also shows that skin arterioles in SHR are more responsive to local temperature changes.

Vasodilator Action of Pentoxifylline on Microcirculation of Rat Cremaster Muscle

Pentoxifylline improves microvascular blood flow in conditions of vascular insufficiency. The clinical benefits of pentoxifylline have been attributed to its effects on the cellular elements of whole blood, although a few studies suggest it may also be a vasodilator. The purpose of this study was to determine whether pentoxifylline has a vasodilator effect on the luminal diameter of small arteries preconstricted with norepinephrine and on resting small arteries in the rat cremaster muscle. Intravital videomicroscopy was used in order to observe directly the vasodilator capacity of topically applied pentoxifylline. The results reveal that pentoxifylline (100 microM and more) can significantly dilate small arteries preconstricted with norepinephrine. Pentoxifylline had no effect on the diameter of resting small arteries. These results suggest that vasodilation may play a role in the ability of pentoxifylline to improve arterial blood flow.

Thromboxane A2/endoperoxide receptors mediate cholinergic constriction of rabbit lung microvessels.

Using an X-ray television system, we directly measured the internal diameter (ID; 100-1,000 microns) of small pulmonary arteries and analyzed the effects of cyclooxygenase inhibition and thromboxane A2/prostaglandin endoperoxide (TP) receptor blockade on the ID reductions in response to vagal nerve stimulation (VNS; 16 Hz) and injection of acetylcholine (ACh; 0.3 micrograms) in anesthetized rabbits. The ID reductions of the small arteries in response to VNS and ACh were completely abolished by pretreatment with cyclooxygenase inhibitors indomethacin and meclofenamate. Those reductions were also eliminated by pretreatment with TP receptor antagonists AA-2414 and Ono 3708. Both TP receptor antagonists abolished the ID reduction to thromboxane A2 mimetic U-46619 but did not affect the reduction to norepinephrine. The ID reductions in response to VNS and ACh were eliminated by atropine. The reduction in response to VNS was abolished by hexamethonium bromide, whereas the reduction in response to ACh was not altered by hexamethonium bromide. The results indicate that vasoconstrictions of the rabbit small pulmonary arteries in response to VNS and exogenous ACh are mediated by TP receptors as well as muscarinic receptors. The data suggest that during VNS endogenous ACh acts on muscarinic receptors to constrict the small arteries mainly by generating thromboxane A2 or prostaglandin endoperoxide.

A new vascular prosthesis of bovine origin.

An experimental study on a new biologic vascular graft for reconstruction of small diameter arteries was carried out in 50 sheep. A follow-up period of two years let us conclude that the new vascular prosthesis may be "re-utilized" by the host. Infection and aneurysmatic degeneration could not be observed. An early occlusion of the graft occurred in only one case, due to technical reasons.

An algorithm for angiographic estimation of blood vessel diameter

This study was carried out in an attempt to develop an objective and robust method for measuring changes in the diameters of small blood vessels from X-ray angiographic images. Recognizing potential problems with edge detection methods applied to cylindrical vessels in which the contrast diminishes as the boundary is approached, we have attempted to utilize the X-ray absorbance data across the entire cross section of the vessel. Then, assuming a cylindrical geometry, the absorbance data are fit to the cylindrical absorbance function by use of nonlinear regression analysis. The method was tested and calibrated using glass tubes filled with various concentrations of contrast medium. The diameters of small pulmonary arteries were estimated by applying the method of angiograms obtained from an isolated dog lung lobe. The structure of the residuals obtained after the fitting procedure was analyzed to test the appropriateness of the model for use with images of vessels. The results suggest that this approach will have utility for systematically quantifying vessel dimensions.

Evidence that acetylcholine‐mediated hyperpolarization of the rat small mesenteric artery does not involve the K+ channel opened by cromakalim

1. Acetylcholine causes a concentration-dependent hyperpolarization of the rat small mesenteric artery (diameter at 100 mmHg, 200-400 microns). In the absence of tone the average potential change was from approximately -60 to -75 mV. In the presence of tone induced by endothelin-1 (20 nM), acetylcholine caused vasorelaxation in association with a marked hyperpolarization; from approximately -32 to -71 mV. 2. A number of compounds known to antagonize the actions of cromakalim were tested for their ability to block responses to acetylcholine. Glibenclamide (0.1-3 microM), phentolamine (10-100 microM) and alinidine (1-30 microM) caused a concentration-dependent depolarization of the rat small mesenteric artery which was not dependent on an intact endothelium. Glibenclamide was approximately 10 times more potent than either phentolamine or alinidine, a similar ratio to their potency as antagonists of cromakalim. 3. In the presence of concentrations of the cromakalim antagonists which functionally inhibited responses to cromakalim, only phentolamine and alinidine had a significant effect on the hyperpolarization and functional responses to acetylcholine. Glibenclamide was without effect at the concentrations used. 4. Experiments on pig coronary artery, where acetylcholine causes vasoconstrictor responses, showed that phentolamine and alinidine have some anti-muscarinic activity which could account for their ability to affect vasorelaxant/hyperpolarization responses to acetylcholine in the rat small mesenteric artery. 5. The results suggest that the acetylcholine-mediated hyperpolarization observed in the rat small mesenteric artery does not involve K+ channels opened by cromakalim. This finding differs from other studies performed on the rabbit middle cerebral artery which show hyperpolarizing responses to acetycholine to be glibenclamide-sensitive. It is likely therefore that the hyperpolarization response observed to acetylcholine can be initiated through a number of mechanisms, only one of which utilizes K+ channels opened by cromakalim.

The effect of acute denervation on the microcirculation of skeletal muscle: Rat cremaster model

Although tissue is denervated during replantation of a severed part, tissue transfer, or muscle transplantation, there are few studies concerning the effects of acute denervation on muscle microcirculation. We have described a surgical procedure that totally denervates the rat cremaster muscle. Histological examination of the denervated tissue has given convincing evidence of nerve degeneration and skeletal muscle atrophy, accompanied by electrophysiological evidence of total denervation. The diameters of each component of the microcirculation were measured before and after denervation. Arterioles and arteries ranging in size from 10 to 70 microns in diameter were found to increase significantly in size immediately after acute denervation. Larger arteries and veins did not undergo significant diametrical increases. These findings suggest that total acute denervation significantly increases the diameter of small arteries and arterioles, thereby decreasing the resistance in the arterial bed and increasing blood flow. Since this phenomenon is of limited duration (20 min), it would appear to be ineffective in enhancing reperfusion and oxygenation at the time of reattachment of amputated parts or during vascularized tissue transfers, until methods of prolonging it for several hours or more are found.

Constrictor Response of Small Pulmonary Arteries to Acute Pulmonary Hypertension during Left Atrial Pressure Elevation.

Acute elevations in left atrial pressure (LAP) were induced by altering the volume of air within a balloon inserted into the left atrium; the changes in internal diameter (ID) of small muscular pulmonary arteries (100-600 microns ID) in response to the associated rises of pulmonary arterial pressure (PAP) were measured using an X-ray TV system on the in vivo cat lung. When LAP was elevated to 14 +/- 1, 24 +/- 1, and 30 +/- 1 mmHg, PAP was increased to 21 +/- 1, 30 +/- 1, and 37 +/- 1 mmHg, respectively. With PAP ranging from 16 (control value) to 21 mmHg the ID did not dilate significantly. With PAP of 30-37 mmHg significant ID dilation occurred. The magnitude of the ID dilation (16%) with PAP of 37 mmHg, however, was significantly smaller than that (20%) with PAP of 30 mmHg despite the greater pressure rise. When the elevated PAP of 30-37 mmHg was quickly returned to the control level by rapid balloon deflation, the ID constricted significantly below the control level. The magnitude of the ID constriction was proportional to the degree of the preceding PAP rise and was maximal in the arteries of 200-400 microns ID. A papaverine hydrochloride injection combined with the balloon deflation completely abolished the ID constriction. A phentolamine injection, on the other hand, significantly attenuated the constriction with approximately half of the constriction persisting. The results indicate that an increase in vascular smooth muscle tone occurred in the small muscular pulmonary arteries, particularly those of 200-400 microns ID, in response to the acute rise of PAP above 30 mmHg during the LAP elevation. In addition, the data suggest the partial participation of catecholamines in the active contraction of vascular smooth muscle. The arterial contraction may serve to protect the pulmonary capillaries from an excessive hydrostatic pressure and pulmonary edema.

Vagally and acetylcholine-mediated constriction in small pulmonary vessels of rabbits.

Using a new X-ray TV system, we analyzed effects of vagal nerve stimulation (VNS; 1-30 Hz) and intravenous injection of acetylcholine (Ach; 0.3-0.9 microgram) on the internal diameter (ID; 100-1,500 microns) of small pulmonary arteries and veins in anesthetized rabbits. In selective segments of the arteries, ID decreased abruptly and maximally by 50-70% in a specific stimulus frequency to the vagal nerve and a dose of ACh. The vasoconstrictor sites were distributed near the branching points of the arteries, particularly those downstream, and their numbers increased with an increase in the stimulus frequencies and ACh doses. The relative frequencies of occurrences were 15.3% with VNS (30 Hz) and 5.3% with ACh (0.9 microgram). In nonselective segments with VNS, ID decreased frequency dependently by 0, 4, 12, and 26% at 1, 4, 15, and 30 Hz, respectively, and with ACh, decreased dose dependently by 21 and 35% with 0.3 and 0.9 microgram, respectively. The vasoconstriction in response to VNS and ACh was attenuated by atropine, enhanced by eserine, and not affected by phentolamine. That vasoconstriction to VNS was abolished by hexamethonium. No selective constriction was found in veins and the ID was decreased uniformly by 1-2% with VNS and ACh.

Responses of sequentially branching macro- and microvessels during reactive hyperemia in skeletal muscle

Small artery and microvascular responses during reactive hyperemia were compared to determine which resistance-bearing vessels played a role in controlling blood flow and resistance for the cremaster skeletal muscle. Using an intravital video microscopy system, measurements of microvessel pressure, flow velocity, and diameter were obtained from cremaster muscles in anesthetized rats. These were compared with measurements of diameter that were obtained from the small arteries feeding the cremaster muscle. After a 60-sec occlusion of the sacral aorta, total cremaster blood flow increased approximately 28% and calculated microvascular resistance for the cremaster muscle fell 50%. During the period of occlusion, diameters of small arteries (159–292 μm) decreased despite the presence of smooth muscle tone. Likewise, the diameters of large arterioles (65–117 μm) decreased whereas small arterioles (16–30 μm) dilated. The decrease in diameter of the small arteries and large arterioles was accompanied by a significant fall in intravascular pressure, suggesting that the behavior of these vessels was largely passive. Immediately following the release of occlusion, small arteries and large arterioles returned to their control diameters while small arterioles remained in a dilated state for approximately 2 min. These results indicate that for the cremaster muscle, (1) vascular responses vary along the length of the arterial tree during reactive hyperemia, (2) small but not large arterioles are primarily responsible for the decrease in network resistance and subsequent hyperemia following occlusion, and (3) the small feeder arteries did not dilate during reactive hyperemia but instead acted to set a limit on the decrease in network resistance and the increase in blood flow.

Conformational stress and anastomotic hyperplasia

Late failure of synthetic vascular grafts to small-diameter arteries (≤4 mm) is commonly due to anastomotic hyperplasia. Theoretic analysis suggests that conformational changes at the anastomosis lead to high localized arterial wall stress caused by increases in radius of curvature of the artery (law of Laplace: tension = pressure × radius). Nine 3 kg rabbits had a plastic insert implanted into the infrarenal aorta. The insert was designed to recreate the conformational changes caused by the anastomosis of a synthetic graft to a small-diameter artery, without significantly altering blood flow. The increase in arterial wall tension created by the insert was calculated to be 80% to 100% over baseline values. Aortography, real-time ultrasound, and computed tomography (CT) scanning were done to confirm the absence of luminal thrombus formation or migration of the insert. Ultrasound and CT scans also confirmed the desired conformational changes in the aorta at the site of the insert. Aortas, with the inserts in place, were removed from 3 days to 6 months after implantation. Implantation times of 1 to 6 months resulted in a hyperplastic subintimal lesion characterized by fibrous tissue deposition, spindle cells (which may have been fibroblasts), and/or smooth muscle cells covered by endothelium. In contrast, two rabbits that had the insert placed and then removed at 1 minute and were allowed to survive for 37 and 72 days, respectively, demonstrated complete healing of the aorta without anastomotic hyperplasia. The arterial wall conformational changes induced in this experiment led to the formation of a lesion consistent with anastomotic hyperplasia. An increase in wall tension may have been the stimulus for this response. Prevention of anastomotic hyperplasia may require a means of uniting a graft to an artery without increasing wall tension.

Regional coronary hemodynamic responses to cold stimulation in patients without variant angina

The responses to cold in patients with exertional chest pain were studied by measuring coronary sinus and great cardiac vein flows, aortic and left ventricular pressure and diameters of epicardial and small (0.4 to 1.0 mm) intramyocardial coronary arteries before and after the left hand of 18 such patients was immersed in ice water. Coronary sinus and great cardiac vein flows were used as indexes of total and anterior left ventricular flows. Coronary sinus flow minus great cardiac vein flow was used as an index of inferior left ventricular flow. Perfusion of left ventricular regions was considered potentially “normal” or “abnormal” according to the presence or absence of 50 percent or greater stenosis of luminal diameter in the coronary artery supplying a given region. With cold stimulation, increases occurred in heart rate (6 beats/min), mean aortic pressure (22 mm Hg) and left ventricular end-diastolic pressure (8 mm Hg) (all p < 0.05). Left ventricular flow in normally perfused regions increased as resistance decreased. Left ventricular flow in abnormally perfused regions increased slightly and resistance increased. Regional left ventricular flow increased more, and changes in resistance differed in normally and abnormally perfused regions. Coronary arterial diameter decreased only minimally (6 percent) in both normal and abnormal left ventricular regions. These data show that cold stimulation increases coronary resistance in abnormally perfused left ventricular regions. Cold stimulation-related increases in coronary resistance do not appear to be caused by coronary arterial “spasm”.

Response of Small Arteries in the Rat Cremaster Muscle to Decreases in Perfusion Pressure

The diameters of the small arteries feeding a microcirculatory bed are determined by the interaction of a number of controlling factors. Neural, humoral, and physical factors all interact to modulate the arterial diameter based on the prevailing local and systemic conditions. The neural and humoral systems are undoubtedly active mechanisms involved in feedback control systems to regulate tissue flow. However, changes in diameter as a result of physical forces, namely, changes in intralumenal pressure, may simply be a local response resulting from changes in vessel wall stresses. There are a number of experimental and pathological conditions in which studies of microvascular diameters are accompanied by significant decreases in systemic pressure. For example, previous studies (1,2) have shown that severe systemic hypoxia in the rat produced a substantial decrease in arterial pressure, and direct measurement of small artery diameters in the rat cremaster muscle showed significant decreases in diameter durin...

Modification of α-adrenergic responses of small arteries by altered PCO 2 and pH

Closed-circuit television microscopy was used to measure in vivo small artery (75–140 μ) and vein (105–230 μm) diameters to determine if changes in tissue PCO 2 and/or pH would alter the microvascular responses to norepinephrine. Sprague-Dawley rats were anesthetized with a combination of urethane (800 mg/kg) and α-chloralose (60 mg/kg). The cremaster muscle with intact circulation and inervation was suspended by sutures in a 60-ml bath which contained and mofified Krebs solution (31°C) that was buffered by Tris of bicarbonate. There were four groups of animals with different combintions of bath PCO 2 and pH: (1) PCO 2 < 10 mm Hg and pH = 7.2, PCO 2 < 10 mm Hg and pH = 6.9, (3) PCO 2 = 60–70 mm Hg and pH = 6.9. The maximal responses of the small artery and vein to norepinephrine were similar for the four groups. The artery sensitivity to norepinephrine was signficantly lower for group 4 when compared to groups 1, 2 and 3, but there was no effect on small vein sensitivity. This, the combination of decreased pH and increased PCO 2 reduces small artery sensitivity to norepinephrine in the cremaster muscle of the rat.