Benign Hypertension Research Articles

Bioassay by cross-perfusion for circulating inotropic factor in hypertension

To study inotropic effects of blood from one-kidney, one-clip (1K,1C) rats with early (less than 7 days) or chronic (greater than 4 wk) benign hypertension, we assessed arteriolar resistance and norepinephrine (NE) responses in vascularly isolated, innervated assay hindlimb vascular beds of alpha-chloralose-anesthetized, normal male recipient rats. Hindlimbs were cross-perfused (2 ml/min) with blood from anesthetized donor rats with limb outflow returned to the donor rat. Perfusion pressure was monitored. Complete NE (injected intra-arterially) dose-response curves in limbs perfused with donor blood from nine early 1K,1C rats, compared with nine appropriate normotensive control donor rats, indicated unchanged thresholds, 50% effective doses, and maximal responses. Curves in limbs perfused with blood from 10 chronic 1K,1C, compared with 10 appropriate controls, suggested small (P less than 0.02) leftward shifts. Decreases (P less than 0.01) in maximal responses were also observed. Limb resting resistance and minimal resistance (sodium nitroprusside) did not rise, even after 4-5 h of cross-perfusion. These results provide no evidence in early 1K,1C and little evidence in chronic 1K,1C that humoral factors, including ouabainlike inhibitors, evoke physiologically significant inotropic effects in arterioles in vivo.

Behçet Sendromunda Benign Intrakranial Hipertansiyon ( Vaka Takdimi )

SUMMARY Benign Intracranial Hypertension in Behcet Syndrome (Case Report) Two patients with Behcet's disease presenting as benign intracranial hypertension are reported and the literature is reviewed in this paper. We suggest that benign intracranial hypertension is not rare in Behcet's disease. For this reason a careful history and examination for evidence of Behcet's disease should be undertaken in patients who have findings of benign intracranial hypertension.

Predisposing Factors for the Development of Malignant Essential Hypertension

To clarify predisposing factors for malignant hypertension, we retrospectively investigated the histories of 39 patients with malignant hypertension and 39 patients with benign hypertension. Between the malignant and benign groups, there was a statistically significant difference in blood pressure but not in age when hypertension was first noticed. The number of patients who had discontinued drug treatment was significantly greater in the malignant group (19; 49%) than in the benign group (11; 28%). Insufficient sleep, overwork, and/or mental burden of long duration were factors noticed within one year before the occurrence of the malignant phase in 11 (37%) of the 30 patients in that group in whom this information was available. Patients in the malignant group tended to belong to a lower social class. These results suggest that severe hypertension from an early phase, interruption of drug treatment, and physical and/or mental burden may predispose to the development of malignant hypertension, and that these predisposing factors are likely to be associated with social class.

Motor neuron disease in the United States, 1971 and 1973-1978: patterns of mortality and associated conditions at the time of death.

Mortality rates for deaths "due to" and "with" motor neuron disease are presented for the first time. Age-specific mortality rates increase with age until 70 to 74 years and then decline. There appear to be no major differences by race in the age-adjusted mortality rates, but these rates are higher for males both white and nonwhite. A case-control study of all deaths with amyotrophic lateral sclerosis (ALS) was conducted for deaths due to ALS in the year 1971. Conditions associated with ALS at the time of death include pneumonia and bronchopneumonia, symptoms referable to respiratory system, superficial injury to shoulder and upper arm, essential benign hypertension, chronic skin ulcer, and malnutrition. No association was found between ALS and malignancies, Parkinson's disease, or dementia.

Mitochondrial aspartate aminotransferase linked to immunoglobulin G of the κ- λ type: report of a case

Macromolecular aspartate aminotransferase ( l-aspartate: 2-oxoglutarate aminotransferase EC 2.6.1.1, AST) was found in the serum of a patient with benign hypertension. The serum total AST and mitochondrial AST (mAST) activities were proportionately higher. The abnormal AST was found to be a macromolecular complex composed of mAST and immunoglobulin G of the κ-λ type. The dissociated IgG from the complex was shown to combine with human and rat mAST, but not with cytosolic AST of both species. Molecular mass of the macromolecular AST was estimated to be 360000 Da. These results indicate that the complex may consist of one IgG molecule associated with two mAST molecules. By the method of papain digestion the binding site of immunoglobulin in the complex appeared to be located in the Fab portion of the IgG molecule. This finding strongly suggests that the AST-immunoglobulin complex is a specific antigen-antibody complex.

Different cation transport inhibitor in benign and malignant experimental renal hypertension.

The role of circulating humoral agents in the pathogenesis of abnormal vascular wall cation composition in benign and malignant renal hypertension was investigated. Male F344 rats with chronic benign (n = 38) and malignant (n = 44) one-kidney, one clip (1K1C) hypertension and normotensive control rats (n = 63) were studied. Malignant hypertension developed spontaneously and was characterized by failure to thrive, weight loss, oedema, renal insufficiency, anaemia or haemoconcentration and hyperkalaemia. For bio-assay, monolayers of quiescent vascular smooth muscle cells from F344 rats were incubated in plasma or plasma extracts of normotensive and hypertensive rats for measurement of labelled rubidium (86Rb) uptake in the presence and absence of 2 mmol/l ouabain and/or 1 mmol/l furosemide. Compared with controls, ouabain-sensitive Rb uptake of cells was reduced in plasma extracts but not in whole plasma of rats with benign hypertension. Ouabain-sensitive Rb uptake was unchanged and ouabain-insensitive Rb uptake was reduced in both plasma and plasma extracts of rats with malignant hypertension. The latter was due to a reduction in furosemide-sensitive Rb uptake. In malignant hypertension, the increased sodium (Na) content of the aorta which characterizes benign hypertension was reversed and bladder wall Na content was reduced. The findings suggest that in malignant hypertension a circulating, furosemide-like inhibitor of ouabain-insensitive cation transport is the cause of vascular wall Na depletion and of diuresis and natriuresis that trigger the syndrome.

Who Should Do the Coding?-Reply

In Reply.— We disagree with Dr Solomkin that the missing information discovered in our study is an administrative problem. Improvement in data bases such as the Veterans Administration's Patient Treatment File requires support from both clinical and administrative services. We attempted to attribute errors to their source. Coding is based on the Discharge Summary and Operative Reports. Because the physician is responsible for these documents, we considered missing information in these reports to be the physician's responsibility. Using Dr Solomkin's example of benign hypertension, we do not agree that it is an insignificant diagnosis. Furthermore, it is not appropriate to make an administrative decision that a patient had hypertension and to add it to the discharge summary. We agree that many of the omissions found were of lesser significance. However, many were important, both clinically and financially. Our protocol for inclusion of a diagnosis was that it was treated, that

Prevalence of circulatory disease among patients undergoing intracapsular cataract extraction.

Prevalences of 15 circulatory diagnoses were investigated for 113,242 patients undergoing intracapsular cataract extraction and 67,052 reference patients discharged from a sample of North American hospitals during 1979. After controlling for distributional differences in age (nine categories between 45 and 89 years), sex, and race (white v nonwhite), seven of the 15 diagnoses occurred with sufficient frequency to allow age-, sex-, and race-adjusted analysis. All seven of those diagnoses were found to have statistically significant differences in prevalences between the two procedure groups. Only benign hypertension was found to be more prevalent among patients undergoing cataract extraction regardless of age, sex, or race. The remaining six diagnoses all had a pattern of elevated prevalence among younger patients undergoing cataract extraction changing to elevated prevalence among other surgical patients at older ages.

Examination of the fundus of the eye of renal hypertensive dogs.

Only 1 of 7 dogs with long-standing renovascular hypertension showed clear changes in the fundus. No distinct retinopathy was seen in the others. Ophthalmoscopy alone is thus of limited value in assessing the progress of benign hypertension in the dog.

Cerebrospinal fluid lactate and pyruvate concentrations in patients with malignant hypertension.

Lactate and pyruvate concentrations and acid-base parameters in cerebrospinal fluid (CSF) and arterial blood were measured in 21 patients with malignant hypertension ( MHT ), 19 with benign hypertension (BHT) and 21 normotensive subjects (NT). Average values for CSF lactate and lactate/pyruvate (L/P) ratio were significantly higher in MHT (1.90 +/- 10 mM/1, 19.2 +/- 1.0) than in either BHT (1.50 +/- 0.05 mM/l, 15.7 +/- 0.7) or NT (1.44 +/- 0.04 mM/1, 15.7 +/- 0.4). There was a linear correlation between CSF lactate and CSF pressure (r = 0.565, P less than 0.01), and the latter was also related to mean arterial pressure exceeding 150 mm Hg (r = 0.553, P less than 0.01). Such increases in the acid metabolites in CSF indicate that brain metabolism becomes anaerobic in MHT , probably due to increased intracranial pressure. Increased cerebrovascular permeability is also discussed as participating in causal mechanisms.

Malignant hypertensive crisis induced by chronic intrarenal norepinephrine infusion.

The purpose of the present study was to develop a controllable experimental model in the dog that would consistently and predictably produce a malignant hypertensive crisis, and to determine the sequential changes in renal function, salt and water balance, and hormones that are involved in the transition from benign to accelerated hypertension. Norepinephrine (NE) was infused continuously into the renal artery of unilaterally nephrectomized dogs that were maintained on 50 mEq sodium/day. The infusion rate of NE was increased each day according to the following schedule: 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 microgram/kg/min. During the first 4 to 5 days of intrarenal NE infusion, there was a progressive decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), and increases in plasma renin activity (PRA), mean arterial pressure (MAP), and filtration fraction. At the end of this period of benign hypertension, MAP had risen from a control value of 91 +/- 4 to 132 +/- 8 mm Hg, in association with approximately a 10-fold increase in PRA and a 40% reduction in renal function. Then, suddenly, during the subsequent 24-hour infusion period, the MAP increased abruptly in all animals (MAP = 156 +/- 8 mm Hg), and a hypertensive crisis occurred. This crisis was associated with the following: salt and water depletion, hyponatremia, hypovolemia and hemoconcentration, polydipsia, marked activation of the renin-angiotensin-aldosterone system, increased plasma cortisol concentration, hemolysis, marked impairment in renal function, lethargy, and vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities of vascular wall sodium content in dogs with benign and malignant renal hypertension.

The water and sodium content of the saphenous vein was measured in 26 dogs with one-kidney, one wrapped hypertension. For comparison, the same measurements were performed on the contralateral saphenous vein which was removed prior to the induction of hypertension. Malignant hypertension characterized by blindness and a rise in plasma renin activity, developed in 10 dogs. The course of hypertension in the remaining 16 dogs was benign. In benign hypertension, the water and sodium content of the saphenous vein was increased. In contrast, the water content of the saphenous vein was unchanged and its sodium content fell in dogs with malignant hypertension. The dogs with malignant hypertension had a greater sodium content of the saphenous vein prior to the induction of hypertension than the dogs with benign hypertension. The findings indicate that the loss of body water and sodium that has been described in malignant hypertension also affects the composition of blood vessels. The sodium content of blood vessels may be a predictor of the dog's response to a hypertension-producing stimulus.

Acute arterial fibrinoid deposition and ischaemic parenchymal damage of the kidney. Pathogenic factors in the development of malignant hypertension.

The development and evolution of hypertensive vascular lesions affecting the arterial supply of (a) the kidney and (b) organs other than the kidney were studied in rats developing either malignant (MHY) or benign (BHY) hypertension 3, 6, 9 and 12 days after aortic ligation between the renal arteries. Vascular disease evolved into two distinct patterns which suggested acute renal damage to be the determinant for the development of either the malignant or benign form of hypertension. Three days after aortic ligation MHY and BHY animals showed widespread fibrinoid deposition in vascular territories above the aortic ligature. However, in MHYs these lesions were much more severe and, in the kidney, they were accompanied by the development of focal parenchymal atrophy, microinfarcts and hyalin droplet degeneration of cells of the Bowman capsule. The degree of renal damage correlated with elevations in blood urea nitrogen (BUN) and plasma creatinine; however, there was no correlation with rises in blood pressure, plasma renin activity (PRA), aldosterone or corticosterone which were similarly elevated in 3-day MHY and 3-day BHY animals. Between 6 and 12 days a marked clearance of fibrinoid took place in all organ beds of BHYs, but in the non-renal vasculature of MHY animals fibrinoid remained prominent and served as the central core for necrotising arterial lesions. In the kidney of MHYs some reduction in the fibrinoid content was observed, but the parenchymal damage perpetuating from the earlier stages had exacerbated leading to collagen deposition and a marked increase in the collagen concentration of the renal cortex. These features were accompanied by further elevations in PRA and corticosteroids and a progressive deterioration of renal function. By contrast, in 12-day BHY animals, despite sustained hypertension, PRA and corticosteroids were falling from their previously higher levels and normal renal function was maintained. These studies warrant inference that extensive parenchymal damage of the kidney due in part to severe arterial fibrinoid deposition is one of the initial events in the development of malignant hypertension.

Amaurosis fugax. A unselected material.

Forty-four unselected patients with amaurosis fugax (AF) have been followed for 4.6 years (mean 2.6). Thirty per cent had atheromatous lesions, 20% had miscellaneous diagnoses (temporal arteritis 5, transitory ocular hypertension 2, glaucomatous iritis 1, benign intracraniel hypertension 1), 50% consisted of young, mainly women, in whom no cause was found. Prior to AF 2 had hemiplegia, 4 TCI, one optic atrophy and suspicion in 3. None died, one developed hemiparesis and one macular degeneration. An individual conservative attitude to AF seems justified in this material.

Malignant hypertension: cardiac structure and function at presentation and during therapy.

We have studied electrocardiograms, chest radiographs, and digitised apex echocardiograms in 16 patients with malignant hypertension before and after up to six months of antihypertensive treatment and compared them with those of eight patients with severe benign hypertension. Adequate blood pressure reduction was obtained in 14 with resolution of retinopathy, but one patient died and another had poor blood pressure control. Nine had electrocardiographic criteria of left ventricular hypertrophy which did not change with treatment and 10 had lateral ischaemia which resolved in seven. The malignant hypertensives were divided into seven with and nine without a previous hypertensive history. Both groups had normal echocardiographic cavity dimensions, but the former group tended to have hypertrophy (similar to that in benign hypertensives) and the latter did not. After adequate reduction of blood pressure, no change in wall and septal thickness occurred (except in one patient with poor blood pressure control). At entry, malignant hypertensives showed delayed mitral valve opening with significant cavity dimension increase during prolonged isovolumic relaxation, reduced peak rate, and prolonged duration of cavity dimension increase and cavity shape change (inward wall motion) during the upstroke of the apexcardiogram which showed a tall "a" wave. After reduction of blood pressure, though the delay in mitral valve opening persisted, the timing of A2 returned towards normal and the dimension change during the upstroke of the apexcardiogram and the relative height of the "a" wave were reduced but remained significantly different from normal. Some patients without a previous hypertensive history may develop a malignant phase without left ventricular hypertrophy on the electrocardiogram or echocardiogram. They maintain their pump function even with radiological pulmonary oedema, have incoordinate relaxation and contraction, and have abnormal filling. Similar functional abnormalities were found in malignant hypertensives with hypertrophy. Treatment to reduce blood pressure reduces incoordinate contraction, but impaired diastolic function persists as in benign hypertension, suggesting that these abnormalities are the result of altered myocardial properties that may occur without hypertrophy.

RENAL VASCULAR LESIONS IN SEVERE HYPERTENSION

Renal vascular changes in severe hypertension were studied. Twenty-five cases selected from 4,629 autopsies were classified into 2 groups according to the cause of death: group 1 (9 cases died of renal failure) and group 2 (16 cases of extra-renal death). Group 1 had been clinically diagnosed as malignant hypertension and had the hallmarks of malignant nephrosclerosis characterized by arteriolar fibrinoid necrosis and edematous intimal thickening. Group 2 had been clinically diagnosed as benign hypertension and basically exhibited the changes of benign nephrosclerosis. However, about half of the cases of group 2 had arteriolar fibrinoid necrosis, though the lesion was usually less extensive than in group 1. Immunofluorescence revealed similar deposits of immunoglobulins and fibrinogen in the site of fibrinoid necrosis observed in both groups. As for the changes of interlobular arteries, a quantitative analysis disclosed a distinctive difference between groups 1 and 2 with respect to the narrowing ratio of arterial lumina, though edematous intimal thickening was recognized on relatively rare occasions in the distal interlobular arteries in a few cases of group 2. From the results, the problem of transition from the benign to malignant nephrosclerosis was discussed.

Hemodynamic mechanism of blood pressure response to captopril in human malignant hypertension.

The hemodynamic mechanism of blood pressure response to angiotensin blockade is well established in "benign" but not in human malignant hypertension. We studied the changes in mean arterial pressure (MAP), cardiac index (CI), pulmonary wedge pressure (PWP), and in plasma volume (PV) induced by a single oral dose of captopril (150 mg) in 11 patients with malignant hypertension. Two hours after captopril, MAP fell from 178.5 +/- 5.8 to 151.8 +/- 7.8 mm Hg (p less than 0.001) (means +/- SEM) due to a fall in total peripheral resistance (TPR) (from 54.8 +/- 6.8 to 46.4 +/- 1.6 arbitrary units, p less than 0.001). However, there was a simultaneous increase in CI (from 3.29 +/- 0.13 to 3.70 +/- 0.15 liter/min/m2, p less than 0.001), and a decrease in PWP (from 15.3 +/- 3.5 to 11.0 +/- 2.5 mm Hg, p less than 0.001), while PV remained unchanged (from 4.02 +/- 0.26 to 4.12 +/- 0.12 liters, n.s.). Our data show that, in human malignant hypertension, blood pressure response to captopril is due to a decrease in TPR, but in contrast to benign hypertension, there is also a simultaneous increase in CI. Our results suggest that, in malignant hypertension, potentially high CI levels are artificially normalized by the increased TPR and may be fully disclosed by vasodilation.

Differing patterns of altered glucocorticoid secretion in experimental malignant and benign hypertension. Influences upon the lymphoid system and on arterial connective tissue metabolism.

AbstractAlterations in plasma glucocorticoid levels and in the evolution of the thymus gland were studied in groups of malignant (MHY) and benign (BHY) hypertensive rats sacrificed at 6, 9, 12 and 24 days after aortic ligation between the renal arteries. Although the degree of blood pressure elevation was similar in MHY and BHY animals, MHYs were characterised by severe weight loss, increased plasma renin activity and elevated blood urea nitrogen. MHY animals sacrificed at day 6 showed markedly increased plasma corticosterone (PC) levels (PC: 604 ± 3·9 μg/dl) accompanied by severe thymus atrophy (123 ± 19 mg). In 6‐day BHY animals elevated plasma corticosterone and thymus atrophy were also present but were not as marked as in MHY (BHY: PC: 38·8 ± 4·6 μg/dl, thymus wt: 244 ± 33 mg). Values from BHYs were, however, significantly different from sham‐operated (Sham‐op) controls (Sham‐op: PC: 22·6 ± 1·4 μg/dl; thymus wt: 631 ± 32 mg). In BHY animals sacrificed at day 9, plasma corticosterone had returned to baseline levels. From this time period onward, in BHY animals normal plasma corticosterone was accompanied by a steady recovery of the thymus gland, generalised lymphoid proliferation, and by the proliferation of collagen and elastin (measured by the in‐vitro incorporation of 14C‐l‐proline into both proteins) in the intima‐media and adventitia of the thoracic aorta. Contrary to the normalisation of plasma corticosterone and thymus recovery observed in BHYs, corticosterone remained chronically elevated in MHYs and thymus atrophy was present throughout the entire evolution oif the disease. In MHYs, the arterial connective tissue proliferation was repressed and the synthesis of collagen and elastin was similar to normotensive controls. A. Statistically significant decrease in collagen concentration was present in both intima‐media and adventitia of MHYs when compared to either BHMs or normotensive controls. Impaired vascular hypertrophy in MHYs coexisted with marked alterations in the lymphoid system. In the thymus severe atrophy, thymocyte depletion and a reverse corticomedullary pattern were observed. When the thymocytes remaining in the organ were challenged with the T cell mitogen concanavalin A they showed an impaired proliferative response. In the blood a significant reduction in circulating lymphocytes and marked neutrophilia were observed. These findings suggest that increased glucocrticoid secretion marks important modifications in cells and tissues involved in the production of necrotising arterial lesions during the evolution of malignant hypertension.

Glucocorticoid Hypersecretion and Hypertensive Vascular Disease in Experimental Malignant Hypertension in Rats

1. Changes in plasma glucocorticoid levels and the alterations they imposed upon the lymphoid system and vascular hypertrophy were studied in rats developing either the benign or malignant forms of hypertension during the initial 30 days after aortic ligation. 2. A threefold increase in plasma corticosterone was observed during both the acute and chronic phases of malignant hypertension, whereas in benign hypertension, after a short-lasting twofold increase, corticosterone returned to normal within 9 days. 3. Thymus atrophy, thymocyte depletion and impaired thymocyte reactivity characterized the acute phase of benign and malignant hypertension. After 9 days these alterations receded in benign hypertension, whereas they were permanent features accompanied by severe lymphocytopenia and marked neutrophilia in malignant hypertension. 4. Syntheses and contents of collagen and elastin were impaired in the arteries of malignant hypertensive rats. In contrast, elevated synthesis and increased deposition of these proteins were observed in benign hypertensive rats. Both forms of the disease were characterized by increased deposition of arterial non-fibrous protein. 5. Although acute arterial fibrinoid deposition was observed in benign and malignant hypertension, fibrinoid disappeared in benign hypertensive rats whereas it evolved into necrotizing lesions characterized by disruption of the arterial structure and lymphoid cell infiltration in malignant hypertensive rats. 6. These studies indicate that differing patterns of altered glucocorticoid secretion accompany the development of benign and malignant hypertension. These hormones, by altering the lymphoid system and arterial connective tissue metabolism may participate in the development and perpetuation of the necrotizing arterial lesions observed in malignant hypertension.

Echocardiographic features of malignant hypertension.

Computerised apex- and echocardiography was used to study left ventricular dimensions and function in 13 patients with untreated malignant hypertension and eight with severe benign hypertension. All patients had normal left ventricular cavity dimensions. Five benign hypertensives and malignant hypertensives with a previous history of hypertension had significant thickening of the septum and posterior wall. In eight malignant hypertensives without a previous history wall thicknesses were normal. The absence of ventricular hypertrophy in some cases of malignant hypertension suggests that it is sometimes of rapid onset and not preceded by a non-malignant phase. although fractional shortening and peak Vcf were normal in all the hypertensives, diastolic left ventricular function was frequently abnormal with delayed mitral valve opening, reduced peak rate of filling, and outward endocardial motion during isovolumic relaxation. Malignant hypertensives showed a cavity shape change during isovolumic contraction, and in those without a previous history the aortic second heart sound occurred earlier. The abnormalities of function are probably the result of a combination of factors including pressure overload, abnormal myocardial properties, and myocardial ischaemia, either regional or generalized and secondary to arteriolitis.