Hypertensive Vascular Disease Research Articles

Basic Fibroblast Growth Factor Alterations During Development of Monocrotaline-Induced Pulmonary Hypertension in Rats

The chemical signaling pathways which orchestrate lung cell responses in hypertensive pulmonary vascular disease are poorly understood. The present study examined temporal alterations in lung basic Fibroblast Growth Factor (bFGF) in a well characterized rat model of monocrotaline (MCT)-induced pulmonary hypertension. By immunohistochemical analysis, there were progressive increases in bFGF in airway, vascular and gas exchange regions of MCT-treated rat lungs. Increases in bFGF preceded the onset of right ventricular hypertrophy at day 21 after MCT administration. Enhanced bFGF immunostaining was observed as early as day 4 in focal areas of the parenchyma, and by day 14 there was enhanced bFGF staining in alveolar macrophages, neutrophils and alveolar septa, which persisted through day 21. In conducting airways, there was elevated bFGF immunostaining in the smooth muscle cell (SMC) layer by days 4 and 7 and in the ciliated epithelium and its basement membrane at days 14 and 21. Cells morphologically similar to Clara cells in the luminal surfaces of bronchioles stained intensely on days 14 and 21. In the nucleus and cytoplasm of medial SMCs within pulmonary arteries, there was a progressive increase in bFGF staining starting at day 4. Lung bFGF mRNA was increased slightly at days 1, 4 and 7, while lung bFGF protein, as judged by western blot analysis, was increased at days 14 and 21 compared to controls. The present results, considered in teh light of teh documented roles of bFGF in vascular cell migration, growth and synthesis of extracellular matrix components, suggest that bFGF may contribute to the structural remodeling processes underlying the development of chronic pulmonary hypertension in MCT-treated rats.

The role of platelets in essential hypertension.

Recent research is helping us understand the complex interactions that occur between platelets and their environment. The several intracellular events that occur during platelet activation are being identified as ar their effects on other platelets, the endothelium and coagulation factors. Heightened platelet activation is seen early in essential hypertension and probably plays an important role in the initiation and progression of atherosclerosis and the disorders associated with it. This review identifies some of the changes in platelet structure and function in essential hypertension and their role in the pathogenesis of hypertensive vascular disease.

Pulmonary hypertension in a murine model of the acquired immunodeficiency syndrome.

Rapidly accumulating evidence suggests that a proportion of patients with acquired immunodeficiency syndrome (AIDS) develop hypertensive pulmonary vascular disease reminiscent of primary pulmonary hypertension. As an initial step to explore the link between AIDS and hypertensive pulmonary vascular disease, the present study determined whether pulmonary hypertension is present in a well-characterized murine model of retrovirus-induced immunodeficiency. In agreement with previous reports, mice infected with the LP-BM5 murine leukemia virus developed polyclonal B and T cell activation followed by progressive and severe B and T cell immunodeficiency. At 12 wk postinfection, when persistent immunodeficiency was established, mice were anesthetized, and right ventricular systolic pressure was determined in open-chest, mechanically ventilated animals. Mean right ventricular systolic pressure was 14.7 +/- 1.3 mm Hg in control animals and was increased significantly to 22.5 +/- 3.2 mm Hg in virus-infected mice. Right ventricular hypertrophy was also present in infected mice as evidenced by a 27% increase in the ratio of right to left ventricular weights; there were no group-dependent differences in the left ventricular to total-body weight ratio. Morphometric evaluation indicated that medial thickness in muscularized pulmonary arteries, expressed as a percentage of the external diameter, was 9.6 +/- 0.4% in control lungs and increased to 14.4 +/- 0.5% in lungs from infected animals. Qualitative histopathologic analysis suggested increased perivascular collagen deposition in lungs from infected animals relative to control animals. Unlike AIDS patients with pulmonary hypertension, infected mice did not exhibit plexiform lesions or intimal fibrosis of the pulmonary arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Multiple polyamine transport pathways in cultured pulmonary artery smooth muscle cells: regulation by hypoxia.

The polyamines putrescine (PUT), spermidine (SPD), and spermine (SPM) are a family of low molecular weight organic cations that play essential intracellular regulatory roles in cell growth and differentiation. Consistent with this important function, increases in cellular polyamine contents are necessary for a variety of physiologic and pathologic events in the lung, including development of hypertensive pulmonary vascular disease secondary to chronic alveolar hypoxia. In intact rat lungs, hypoxia depresses ornithine decarboxylase activity, the initial rate-limiting enzyme in de novo polyamine synthesis, and enhances uptake of PUT from the vascular compartment, thus suggesting that increased polyamine transport is the driving mechanism behind hypoxia-induced increases in lung polyamine contents. Cultured bovine pulmonary artery smooth muscle cells (PASMCs) also express a transport system for SPD that is augmented by culture under hypoxic conditions. Because there may be multiple uptake pathways that are relatively selective for specific polyamines, the present study determined whether cultured bovine PASMCs expressed discrete transporters for [14C]PUT, [14C]SPD, and [14C]SPM, and whether they were differentially regulated by hypoxia. [14C]PUT, [14C]SPD, and [14C]SPM transport was examined in PASMCs cultured under "standard" (culture medium PO2: > 100 torr), "normoxic" (culture medium PO2: 50 to 70 torr), or "hypoxic" (culture medium PO2: 18 to 30 torr) conditions. Uptake of all three [14C]polyamines in cells cultured under standard conditions was temperature- and concentration-dependent, exhibited saturation kinetics, and could be modeled by Michaelis-Menten kinetics. In hypoxic PASMCs, values of Vmax for PUT, SPD, and SPM uptake increased by 3-, 2-, and 2-fold, respectively, relative to cells cultured under normoxic or standard incubator conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

The evolution of surgery for renovascular occlusive disease.

Renal artery stenotic disease is the most common form of surgically correctable hypertension. Occlusive lesions of the renal artery are categorized as: arteriosclerotic, fibrodysplastic (intimal fibroplasia, medial fibrodysplasia, perimedial dysplasia) and developmental. The incidence of stroke, heart disease and renal failure has been reduced with contemporary drug management of hypertensive vascular disease, but similar salutary outcomes have not accompanied the medical treatment of renin-mediated renovascular hypertension. Selection of patients for operation implies documentation that a renal artery stenosis is of functional importance. Advances in the surgical management of renovascular hypertension have evolved over the past 50 years, such that carefully performed reconstructions benefit 85-95% of properly selected patients.

1,25-Dihydroxyvitamin D as a Cardiovascular Hormone Effects on Calcium Current and Cytosolic Free Calcium in Vascular Smooth Muscle Cells

Clinical and in vitro evidence suggests a role for the calcium regulating hormone, 1,25-dihydroxyvitamin D (1,25D) in human and experimental hypertension. To establish the cellular basis for this association, we utilized the whole-cell version of the patch clamp method and fluorescence spectroscopic techniques to measure voltage-dependent calcium channel activity and cytosolic free calcium concentrations ([Ca2+]i) in rat tail artery-derived smooth muscle cells, before and after the addition of 1,25D. 1,25D significantly increased the calcium channel current over the range of test pulses, from -40 to +60 mV, in a dose- and time-dependent manner, appearing by 5 to 10 min of exposure, with maximum effects by 15 min. At 10 and 30 nmol/L, the current increased to 149 +/- 10% and 221 +/- 13% of basal activity of 37.75 +/- 7.7 pA and 37.7 +/- 4.5 pA, respectively. Similarly, at 10 and 100 nmol/L, 1,25D increased cytosolic free calcium levels 115 +/- 2% and 171 +/- 11%, from basal values of 99 +/- 32 nmol/L and 116 +/- 10 nmol/L, respectively. These effects of [Ca2+]i developed slowly over 3 to 4 min. Peak values were achieved by 30 min of incubation and were reversible with removal of 1,25D from the medium. Altogether, these direct effects of 1,25D on calcium current and [Ca2+]i in vascular smooth muscle cells support a role for 1,25D in vascular physiology, and provide a cellular basis for better understanding the involvement of 1,25D in hypertensive vascular disease.

In vitro perfusion studies of resistance artery function in genetic hypertension.

To examine the function of resistance-sized arteries in hypertension under in vitro conditions that approximate in vivo conditions as much as possible, we mounted segments of second-order mesenteric resistance arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive control rats aged 12 to 13 weeks in a perfusion myograph and exposed them to conditions of constant flow and pressure. The endothelial integrity was validated both functionally and histologically. Vascular sensitivity to norepinephrine was examined when the hormone was applied either intraluminally or extraluminally and before and after removal of the endothelium. Both endothelium-dependent and -independent dilatation was assessed by the intraluminal application of acetylcholine and sodium nitroprusside, respectively. Sodium nitroprusside was applied to arteries after endothelium removal. Arterial responses were measured by changes in intraluminal diameter recorded with a video camera and imaging system. Vessels from SHR demonstrated depressed endothelium-dependent relaxation but similar endothelium-independent relaxation and greater sensitivity to norepinephrine with both intraluminal and extraluminal application. Removal of the endothelium abolished the differences in sensitivity to norepinephrine between the two strains. The results demonstrate that resistance arteries from SHR when examined under in vitro perfusion display enhanced sensitivity to norepinephrine due to depressed endothelium-dependent dilatation, and the data suggest that functional modifications in the endothelium may play an important role in hypertensive vascular disease.

Potential role of endothelin-1 in the pathogenesis of acute hypertensive vascular disease in the rat

Endothelin-1 (ET-1) is a potent and long-acting vasoactive peptide often implicated in the pathogenesis of hypertension. However, little is known about its role in the pathogenesis of hypertensive vascular disease. This study compares the vascular changes produced in vivo by pressor or subpressor doses of ET-1 and angiotensin II (ANG II) in rat intestinal arterioles. In one experiment, equivalent pressor doses of either ET-1 (0.2 μg/kg/min) or ANG II (2 μg/kg/min) were given. In a second experiment, subpressor doses of ET-1 (10 ng/kg/min) were either infused alone or given in combination with pressor doses of ANG II (2 μg/kg/min). Normal saline infusions (0.02 mL/min) served as controls. All infusions were continued for 60 minutes, interrupted for 30 minutes, and reinstituted for 30 minutes. Changes in vascular permeability were assessed using ferritin as a tracer; vascular lesions were assessed by computerized morphometry and electron microscopy. Results from the first experiment showed that ET-1 and ANG II produced approximately equivalent increases in blood pressure but that ET-1 had more prolonged pressor effects when infusions were interrupted. Pressor doses of either ET-1 or ANG II caused a segmental pattern of vasoconstriction and dilatation, an increase in ferritin permeability, and severe vascular smooth muscle damage. However, vessels from ET-1-treated animals had fewer damaged smooth muscle cells ( p < 0.05) and smaller areas of vessel wall damage ( p < 0.05) than did those from the ANG II-treated group. Subpressor doses of ET-1 in the second experiment produced no vascular lesions, but combined subpressor ET-1/pressor ANG II infusion caused greater hypertension ( p < 0.05) and more extensive damage ( p < 0.01) to greater numbers of vascular smooth muscle cells ( p < 0.01) than did pressor infusions of ET-1 or ANG II alone. The results indicate that subpressor concentrations of ET-1 clearly potentiate the vascular damage caused by ANG II-induced hypertension. On the other hand, pressor doses of ET-1 do not cause more severe vascular injury than do equipresor doses of ANG II, though the hypertension induced by ET-1 has longer-lasting hypertensive effects.

Temporal Alterations in Specific Basement Membrane Components in Lungs from Monocrotaline-treated Rats

The present study utilized the monocrotaline (MCT) model of pulmonary hypertension in rats to examine temporal alterations in steady-state levels of basement membrane (BM) component mRNA and deposition of protein using Northern analysis and immunohistochemistry, respectively. MCT (60 mg/kg, subcutaneous) produced sustained increases in lung dry tissue mass by 7 days, right ventricular mass by 14 days, and pulmonary arterial pressure by 21 days after administration. mRNA levels specific for laminin (LM) were elevated as early as 1 day after MCT treatment, while mRNA for all BM components examined except type IV collagen were increased in lungs from MCT-treated rats by day 4. Differences in LM, perlecan (PN), and type IV collagen-specific mRNAs from lung tissue between MCT-treated and control rats disappeared by day 14. In contrast, fibronectin (FN) mRNA remained elevated in lung tissue from MCT-treated rats from day 4 onward. Increases in immunolocalizable FN and LM in the vasculature, and PN and type IV collagen in gas exchange areas, were observed 4 days after MCT treatment compared with controls. These changes generally became more pronounced by 21 days after MCT administration, at which time the parenchyma of MCT-treated rats also demonstrated increases in immunolocalizable FN, LM, and BM-chondroitin sulfate proteoglycan (BM-CSPG). The pulmonary vasculature additionally showed increases in type IV collagen, PN, and BM-CSPG in MCT-treated rats compared with controls by 21 days. These observations suggest that the accumulation of specific BM components in the pulmonary vasculature and parenchyma may contribute to the pathogenesis and maintenance of MCT-induced hypertensive pulmonary vascular disease.

Thrombotic Lesions in Primary Plexogenic Arteriopathy: Similar Pathogenesis or Complication?

In 78 patients with primary plexogenic arteriopathy (PPA), numbers of organized and recanalized thrombi were established in histologic slides of lung tissue and expressed per square centimeter of section. Three control groups of ten individuals each were used: normal, plexogenic arteriopathy secondary to ventricular septal defect, and hypoxic pulmonary hypertension. Thrombotic lesions were scarce in normal individuals but numerous in all three groups with pulmonary hypertension. There is also a positive correlation with age. Thrombotic lesions are absent or scarce in children but more common in adults, even in normal control subjects and particularly in pulmonary hypertension by whatever cause. In PPA there is likely to be a relation with the duration of illness but not with the stage of the disease. The complete pattern of plexogenic arteriopathy may develop in the absence of thrombotic lesions, which clearly are not essential for its pathogenesis. Rather than being part specifically of PPA, as sometimes suggested, thrombotic lesions complicate various types of hypertensive pulmonary vascular disease. Apparently the combination of sustained pulmonary hypertension and age, possibly through endothelial injury, may elicit thrombosis and its sequelae, which in turn may aggravate the pulmonary arterial pressure.

Platelets, Growth Factors, and Vascular Smooth-Muscle Cells in Hypertension and Diabetes

Inappropriate vascular smooth-muscle cell (VSMC) growth is the hallmark of vascular pathology in essential hypertension and diabetic macroangiopathy, whereas platelets constitute an important regulator of vessel wall homeostasis because of their content of various growth factors. Numerous abnormalities exist in platelet functions in diabetes and hypertension, such as enhanced activity and altered adhesion and aggregation. Increased thromboxane (TX2) production is characteristic of diabetes, and an elevation of intracellular free Ca2+ is found in platelets of hypertensive patients. By studying the growth patterns of VSMC from spontaneously hypertensive rats (SHRs) vs. those obtained from their normotensive counterparts, Wistar-Kyoto (WKY) rats, we have demonstrated that VSMC from SHRs exhibited a higher specific growth rate, abnormal contact inhibition, and accelerated entry into the S phase of the cell cycle. Moreover, they were hyperresponsive to many growth factors such as calf serum, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF beta 1), and insulin. Additive effects were observed for EGF and PDGF or EGF and insulin. These intrinsic growth anomalies in cells of hypertensive origin persist in culture indicating their putative primary role in the pathogenesis of hypertension. Endogenous TGF beta 1 revealed an augmented expression of its message levels in SHR VSMC, the difference in mRNA between both strains being more pronounced at high cell density. Further, TGF beta 1 protein synthesis and secretion in VSMC culture were confirmed by immunoprecipitation of de novo labeled TGF beta 1. At high cell density, which most likely represents the physiological state of VSMC, plasmin, an activator of TGF beta 1, significantly stimulated DNA synthesis of VSMC in both strains. The reverse effect was obtained at low cell density. Yet, the fold stimulation was higher in WKY rats, suggesting that TGF beta 1 may be partially activated in SHR VSMC. This is supported by the inhibition of baseline DNA synthesis by TGF beta 1 neutralizing antibody in VSMC of hypertensive origin and not of normotensive controls. TGF beta 1 antisense oligodeoxynucleotide (ODN) nearly normalized the increased proliferation of SHR VSMC in culture. On the other hand, growth-promoting activity (GPA) in platelets of either diabetic or hypertensive patients was higher than in platelets of healthy controls and was found to be normalized by intensive insulin therapy in insulin-dependent diabetic patients. In hypertensive patients, however, hydrochlorothiazide (HCTZ)--even in low doses (25 mg/day)--enhanced the GPA in platelets, whereas other antihypertensive agents such as indapamide, atenolol, and captopril, had neutral effects.(ABSTRACT TRUNCATED AT 400 WORDS)

The heart in hypertension.

HYPERTENSIVE heart disease can be defined as the response of the heart to the afterload imposed on the left ventricle by the progressively increasing arterial pressure and total peripheral resistance produced by hypertensive vascular disease. Although the response sometimes appears to be out of proportion to the level of the arterial pressure, it is primarily the result of the hemodynamic overload. Hypertension can cause or is related to various cardiac manifestations, among them left ventricular hypertrophy, congestive heart failure, cardiac dysrhythmias, and ischemic heart disease. Although the risk of atherosclerotic coronary heart disease is related to the systolic and diastolic . . .

Stress response pattern in obesity and systemic hypertension

Under resting conditions obese hypertensive patients have been described as having a greater cardiac output and lower total peripheral resistance than lean hypertensive patients. To evaluate the hemodynamic patterns under stress conditions, we determined the hemodynamic response to mental stress (first study) and during isometric exercise (second study) in hypertensive patients with a body mass index >27 kg/m 2 (obese) and <27 kg/m 2 (lean). The cohort exposed to mental stress comprised 54 white male patients (30 were lean, 24 were obese) with untreated stage I or II essential hypertension according to the World Health Organization. Obese subjects responded with a higher increase in total peripheral resistance (p < 0.02) and lower increases in heart rate (p < 0.01), cardiac output (p < 0.01) and stroke volume (p < 0.02) when compared with their lean counterparts. This was independent of any differences in chemical or baseline hemodynamic characteristics at rest. The cohort exposed to isometric stress consisted of 57 patients (30 were lean, 27 were obese) with World Health Organization stage I or II essential hypertension. Obese subjects responded with exaggerated increases in systolic (p < 0.04) and diastolic (p < 0.01) pressures, and heart rate (p < 0.04) when compared with lean patients. Body mass index emerged as an independent determinant of the increase in systolic (r = 0.03) and diastolic (r = 0.01) pressure as well as of heart rate (r = 0.03). These results indicate that obese hypertensive patients respond to (1) mental stress with vasoconstriction instead of the expected vasodilation, and to (2) isometric stress with an exaggerated increase in arterial pressure. These findings argue against the concept that obesity would be prone to mitigate the effects of hypertensive vascular disease.

Influence of hypobaric hypoxia in infancy on the subsequent development of vasoconstrictive pulmonary vascular disease in the Wistar albino rat

A group of Wistar albino rats was injected subcutaneously with monocrotaline to induce vasoconstrictive hypertensive pulmonary vascular disease characterized by medial hypertrophy of small pulmonary arteries, the appearance of muscular pulmonary arterial vessels of arteriolar dimensions (less than 20 microns) in diameter), and exudative changes in the lung parenchyma. The vascular abnormalities were quantified by measuring the percentage medial thickness of small pulmonary arteries, the number of muscular pulmonary arterial vessels below 20 microns in diameter per cm2 of lung section and by determining the smallest arterial vessels in each case showing muscularity. A second group of rats was born in a decompression chamber and kept in hypobaric hypoxia for a month of the neonatal period, developing hypoxic hypertensive pulmonary vascular disease as a consequence. The animals in this group were allowed to recover in room air for a period of 3 months and were then injected with the same dose of monocrotaline as that given to the first group. The rats previously exposed to hypoxia exhibited an exaggerated response to the alkaloid, showing in particular many more small muscular pulmonary arterial vessels which were of a smaller diameter than those found in the eupoxic rats treated with the alkaloid. The experiment demonstrates the perinatal hypoxia exaggerates the effects of agents inducing vasoconstrictive pulmonary hypertension with a shift of the segment of the pulmonary arterial tree involved to the periphery as in hypoxia. Reports of a similar phenomenon are noted as occurring in babies born at high altitude, spending their infancy there and subsequently developing primary pulmonary hypertension later in life.

When is discontinuation of antihypertensive therapy indicated?

Major advances have been established in the handling of hypertensive vascular disease in recent years. However, drug compliance, drug costs, and the side effects of antihypertensive agents have prompted the question of whether intermittent therapy or even possible removal of medication represents an alternative to life-long antihypertensive therapy. Several case reports, and controlled and uncontrolled studies, have focused on this subject, delivering promising but inconsistent results. In this review the attempt is made to clarify the controversial results in order to provide possible selection criteria for patients who can be assumed to benefit from the withdrawal of antihypertensive medication. In addition, the issue of whether a genuine hypertensive can ever become normal is critically reviewed, and an evaluation of the reported success rates is performed. Factors that predicted a successful withdrawal of medication were young age, normal body weight, low salt intake, low pretreatment blood pressure, successful therapy with one drug, and only minimal signs of target organ damage. Additional modification, such as a low-salt or a weight-loss diet, were demonstrated to extend the period of nonpharmacologic treatment. Nevertheless, further studies would be of great help in elucidating how long and how intensively hypertensive patients should be treated before the discontinuation of medication can be tested.

Influence of nifedipine on experimental arteriosclerosis

The nonhemodynamic actions of nifedipine and some other calcium antagonists are reviewed with regard to their relevance to the vasculoprotective and antiarteriosclerotic action of calcium antagonists. Nifedipine, and in order of declining potency, verapamil and diltiazem were shown to inhibit vascular myocyte proliferation and migration. Also, the incorporation of cholesteryl esters into macrophages or myocytes was inhibited by dihydropyridines and verapamil but not by diltiazem. The cholesterol and calcium contents were found to be lowered in the aortae of hypercholesterinemic rabbits treated chronically with dihydropyridine calcium antagonists. Replacement of damaged vascular endothelium and internal elastic lamina was seen in hypertensive Dahl-S rats after 6 weeks of antihypertensive treatment with nifedipine. In addition to their blood-pressure lowering action, these nonhemodynamic effects might be involved in the prevention and reversal of hypertensive vascular disease and neuropathologic symptoms observed after the treatment of hypertensive rats with nifedipine or other dihydropyridine calcium antagonists, since these therapeutic effects were also seen after blood-pressure neutral doses.

Mathematical representation with graphic reconstruction on a microcomputer for an arterial tree

The branching arterial tree is considered as a collection of numerous points and lines. When treated with vertex analysis, it can be expressed with a new mathematical representation, and graphical reconstruction can be carried out on a microcomputer. This new method is useful for recording an arterial tree precisely on anatomical books or comparing arteries under hypertension with those under normotension in order that the early morphological changes of hypertensive vascular disease can be revealed.

Distribution of arterial lesions and collateral pathways in the pulmonary hypertension of congenital heart disease: a computer aided reconstruction study.

Three dimensional computer aided reconstructions of pulmonary vessels were used to investigate the distribution of vascular changes and the formation of collateral channels in 11 patients with congenital heart disease. In the patients with less severe grades of hypertensive pulmonary vascular disease obstructive changes were unevenly distributed, whereas in those with disease of grade 4 or more distribution became more even. Plexiform lesions occurred rather more frequently in supernumerary arteries arising laterally from a large parent vessel, whereas cellular or fibrous intimal thickening tended to affect dichotomous branches at the periphery. Hypertensive changes were confined to arteries of 100-150 microns diameter running along the necks of acini. Various types of collateral channels were found. In particular, the reconstructions suggest that pulmonary arterial blood at high pressure could flow into bronchial arteries via proximal bronchopulmonary arterial anastomoses, and thence by way of dilatation lesions to the alveolar capillaries.

Hemodynamic differences between black patients and white patients with essential hypertension. State of the art lecture.

Physiological studies reported from our laboratory over the past several years have been reviewed and support epidemiological reports indicating that hypertensive cardiac and vascular disease runs a more severe course in the black patient. Although comparison of systemic hemodynamics failed to demonstrate that, for any level of arterial pressure, the magnitude of total peripheral resistance (which is the hemodynamic hallmark of hypertensive disease) differed between black patients and white patients, there are more subtle differences that were ascertained. Thus, although intravascular (plasma) volume contracts as arterial pressure and total peripheral resistance increase in both racial groups, this relation may differ quantitatively. At least in some black patients (43%), intravascular volume may be more expanded; in these patients, this relation is less closely correlated with the renopressor system (i.e., plasma renin activity). Moreover, these studies indicated that, at any level of arterial pressure, cardiac (left ventricular mass and posterior wall thickness) and renal hemodynamic involvement is more severe in the black patient. These findings point to important differences that operate in black patients and white patients with essential hypertension. With further study, these findings may be translated into more specific antihypertensive therapeutic implications for patients of both racial groups with essential hypertension.

In vivo hypertensive arterial wall uptake of radiolabeled liposomes.

Using five sham-operated and seven aortic coarctation-induced hypertensive New Zealand White rabbits intravenously injected with neutral small unilamellar vesicles loaded with [111In]nitrilotriacetic acid, we demonstrated in vivo that the normal aortic arterial wall participates in liposome uptake and that this uptake is increased in the hypertensive aortic wall by approximately threefold (p less than or equal to 0.0001). Among the three regions examined, aortic arch, thoracic aorta, and lower abdominal aorta, the difference in uptake between the normotensive and hypertensive arterial walls was significantly different, p less than or equal to 0.05, p less than or equal to 0.0001, and p less than 0.05, respectively. The uptake by the different regions of the hypertensive arterial wall is consistent with the pathological changes present in these areas. Furthermore, the extent of liposome uptake by the aortic wall is strongly correlated with the height of the blood pressure (r = 0.85, p = 0.001, n = 11). We conclude that neutral small unilamellar liposomes can be used to carry agents into the arterial wall in vivo in the study of hypertensive vascular disease and could be especially useful for the delivery of pharmacologically or biologically active agents that would otherwise be inactivated within the circulation or are impermeable to the arterial wall.