Development Of Malignant Hypertension Research Articles

Imatinib ameliorates renal morphological changes in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

The present study was performed to assess the effects of the platelet-derived growth factor (PDGF) receptor kinase inhibitor imatinib mesylate on the renal morphological changes occurring during the development of malignant hypertension in transgenic rats with inducible expression of the Ren2 gene [TGR(Cyp1a1Ren2)]. Arterial blood pressure was measured by radiotelemetry in male Cyp1a1-Ren2 rats during control conditions and during dietary administration of indole-3-carbinol (I3C; 0.3%) for 14 days to induce malignant hypertension. Rats induced with I3C (n = 5) had higher mean arterial pressures (178 ± 4 vs. 109 ± 2 mmHg, P < 0.001) and increased urinary albumin excretion (Ualb; 13 ± 5 vs. 0.6 ± 0.2 mg/day) compared with noninduced rats (n = 5). Chronic administration of imatinib (60 mg·kg(-1)·day(-1) in drinking water, n = 5) did not alter the magnitude of the hypertension (176 ± 8 mmHg) but prevented the increase in Ualb (1.6 ± 0.3 mg/day). Quantitative analysis of proliferating cell nuclear antigen using immunohistochemistry demonstrated increased proliferating cell number in cortical tubules (38 ± 5 vs. 18 ± 1 cells/mm(2)) and cortical interstitium (40 ± 7 vs. 13 ± 6 cells/mm(2)) of hypertensive rat kidneys. Renal cortical fibrosis evaluated by picrosirius red staining showed increased collagen deposition in kidneys of the hypertensive rats (1.6 ± 0.1 vs. 0.4 ± 0.1% of cortical area). Imatinib attenuated the increase in proliferating cell number in cortical tubules and interstitium (22 ± 5 vs. 38 ± 5 and 22 ± 6 vs. 40 ± 7 cells/mm(2), respectively) and reduced the degree of collagen deposition (0.8 ± 0.2 vs. 1.6 ± 0.1%) in the kidneys of hypertensive rats. These findings demonstrate that the renal pathological changes that occur during the development of malignant hypertension in Cyp1a1-Ren2 rats involve activation of PDGF receptor kinase.

The Role of Endothelial Cell Injury in Thrombotic Microangiopathy

Thrombotic microangiopathy (TMA) refers to a clinical and pathologic syndrome in which endothelial injury results in the manifestations of thrombocytopenia, microangiopathic hemolytic anemia, and kidney injury. A host of causes may induce endothelial injury and TMA, including enteric bacterial toxins, deficiency or dysfunction of complement regulatory proteins, deficiency or inhibition of von Willebrand factor-cleaving proteases, and factors that inhibit endothelial cell proliferation and turnover. This has led specialists to concentrate on these specific inciting factors in terms of designing treatment and management. However, a key and less recognized factor is the underlying level of endothelial health. Many persons with hereditary causes may remain disease free for years or may never develop disease. Others with acute inciting events, such as Escherichia coli O157 enteritis, never manifest TMA. Experimental studies document the importance of specific factors, such as endothelial nitric oxide levels, in helping protect animals from TMA. This suggests that one might approach the management of TMA not simply with specific treatments aimed at the underlying hereditary cause or inciting event, but rather at general measures that may improve overall endothelial health. We propose studies to determine whether interventions that improve endothelial health, such as the administration of angiotensin-converting enzyme inhibitors, statins, vitamin C, allopurinol, or nitric oxide-producing drugs, may be able to prevent TMA, even in persons with underlying hereditary conditions that otherwise would predispose them to these diseases.

Abdominal Aorta Thrombosis Presenting as Headache

Headache is an unusual form of presentation for underlying aortic thrombosis. Thrombosis of the abdominal aorta usually presents with vascular compromise of the lower limbs and presentation, as headache has never been reported. A high index of suspicion and adequate clinical acumen is needed in such cases. CASE REPORT We, report an unusual case of thrombosis of abdominal aorta that presented as headache. Headache is an unusual form of presentation for underlying aortic thrombosis. This 44-yearold non-hypertensive, non-diabetic, non-smoker, average built man sustained minor blunt trauma to abdomen two months ago and was asymptomatic for next one and half month. He presented with sub acute headache of two weeks duration. On admission, patient had blood pressure 240/130mmHg. Fundus examination revealed grade-IV papilloedema with soft exudates and retinal hemorrhages (Figure-1). Figure 1 No other focal neurological deficit was detected. To rule out the possibility of space occupying lesion, CT scan of brain was done and curiously it was normal. Aortic bruit was heard on auscultation. CT Angiography of aorta an intraluminal thrombus with complete occlusion of blood flow involving lower abdominal aorta from the level of origin of renal artery up to its bifurcation and extending into bilateral common iliac arteries.(Figure:2) Figure 2 No flow was seen in left renal artery. The angiographic findings also show the development of sufficient collaterals. The renal functions and other investigations related to hypertension were also within normal limits. Patient was given anti-hypertensive drugs and headache was relieved with control of blood pressure. For further treatment patient was referred to cardio thoracic surgeon. The development of malignant hypertension and secondary papilloedema was probably due to sudden renal compromise and the normal renal functions may be explained due to development of sufficient collaterals. Thrombosis of the abdominal aorta usually presents with vascular compromise of the lower limbs and presentation, as headache has never been reported. A high index of suspicion and adequate clinical acumen is needed in such cases. Abdominal Aorta Thrombosis Presenting as Headache 2 of 3 References Abdominal Aorta Thrombosis Presenting as Headache 3 of 3 Author Information Ch M Sharma Department of Neurology, BMRC, SMS Medical College, Jaipur-Rajasthan (India) BL Kumawat Department of Neurology, BMRC, SMS Medical College, Jaipur-Rajasthan (India) T. Ralot Department of Neurology, BMRC, SMS Medical College, Jaipur-Rajasthan (India) G. Tripathi Department of Neurology, BMRC, SMS Medical College, Jaipur-Rajasthan (India) S. Dixit Department of Neurology, BMRC, SMS Medical College, Jaipur-Rajasthan (India)

Antagonism of endothelin action normalizes altered levels of VEGF and its signaling in the brain of stroke-prone spontaneously hypertensive rat

Stroke-prone spontaneously hypertensive rats (SHRSP) often suffer from spontaneous stroke, in part, due to abnormalities in the cerebrovasculature. Here, we investigate the profile of key angiogenic factors and their basic signaling molecules in the brain of SHRSP during the age-dependent stages of hypertension. The profile of VEGF and its receptor, Flk-1, was dependent on age and stage of hypertension (i.e., down regulated at pre-hypertensive and malignant hypertensive stages, but up regulated at typical hypertensive stage), while that of its downstream components, pAkt and eNOS, were down regulated in a time-dependent manner in the frontal cortex of SHRSP compared to age-matched genetic control, normotensive WKY rats. On the other hand, the expression of endothelin-1 and its type A receptor (endothelin ETA receptor) were up regulated, depending on age and stage of hypertension. In contrast, levels of endothelin type B receptor were down regulated. The regional cerebral blood flow decreased during the development of malignant hypertension. Thus, subsequent experiments were designed to investigate whether endothelin-1 receptor antagonism, using endothelin-A/-B dual receptor antagonist SB209670, could normalize the molecular profile of these factors in SHRSP brain. Interestingly, blockage of endothelin-1 receptor restored to normal, levels of cerebral endothelin-1, endothelin ETA receptor and endothelin ETB receptor; VEGF and Flk-1; endothelial nitric oxide synthase (eNOS) and pAkt, in SHRSP, compared to age-matched WKY. Endothelin receptor blocker might be important to prevent the progression in the defect in VEGF and its angiogenic signaling cascade in the pathogenesis of hypertension-induced vascular remodeling in frontal cortex of SHRSP rats.

Renal vascular and tubulointerstitial inflammation and proliferation in Cyp1a1-Ren2 transgenic rats with inducible ANG II-dependent malignant hypertension

Transgenic rats with inducible ANG II-dependent malignant hypertension [TGR(Cyp1a1Ren2)] were generated by inserting the mouse Ren2 renin gene into the genome of the rat. The present study was performed to assess renal morphological changes occurring during the development of ANG II-dependent malignant hypertension in these rats. Male Cyp1a1-Ren2 rats (n = 10) were fed normal rat food containing indole-3-carbinol (I3C; 0.3%) for 10 days to induce malignant hypertension. Rats induced with I3C had higher mean arterial pressures (173 +/- 9 vs. 112 +/- 11 mmHg, P < 0.01) than noninduced normotensive rats (n = 9). Glomerular damage was evaluated by determination of the glomerulosclerosis index (GSI) in tissue sections stained with periodic acid-Schiff. Kidneys of hypertensive rats had a higher GSI than normotensive rats (21.3 +/- 5.6 vs. 3.5 +/- 1.31 units). Quantitative analysis of macrophage ED-1-positive cells and proliferating cell nuclear antigen using immunohistochemistry demonstrated increased macrophage numbers in the renal interstitium (106.4 +/- 11.4 vs. 58.7 +/- 5.0 cells/mm(2)) and increased proliferating cell number in cortical tubules (37.8 +/- 5.7 vs. 24.2 +/- 2.1 cells/mm(2)), renal cortical vessels (2.2 +/- 0.5 vs. 0.13 +/- 0.07 cells/vessel), and the cortical interstitium (33.6 +/- 5.7 vs. 4.2 +/- 1.4 cells/mm(2)) of hypertensive rat kidneys. These findings demonstrate that the renal pathological changes that occur during the development of malignant hypertension in Cyp1a1-Ren2 rats are characterized by inflammation and cellular proliferation in cortical vessels and tubulointerstitium.

Cyclooxygenase-2 inhibition normalizes arterial blood pressure in CYP1A1-REN2 transgenic rats with inducible ANG II-dependent malignant hypertension

The present study was performed to determine the effects of cyclooxygenase (COX)-1 and COX-2 inhibition on blood pressure and renal hemodynamics in transgenic rats with inducible malignant hypertension [strain name: TGR(Cyp1a1Ren2)]. Male Cyp1a1-Ren2 rats (n = 7) were fed a normal diet containing the aryl hydrocarbon, indole-3-carbinol (I3C; 0.3%), for 6-9 days to induce malignant hypertension. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital sodium-anesthetized Cyp1a1-Ren2 rats during control conditions, following administration of the COX-2 inhibitor nimesulide (3 mg/kg iv), and following administration of the nonspecific COX inhibitor meclofenamate (5 mg/kg iv). Rats induced with I3C had higher MAP than noninduced rats (n = 7; 188 +/- 6 vs. 136 +/- 4 mmHg, P < 0.01). There was no difference in renal plasma flow (RPF) or glomerular filtration rate (GFR) between induced and noninduced rats. Nimesulide elicited a larger decrease in MAP in hypertensive rats (188 +/- 6 to 140 +/- 8 mmHg, P < 0.01) than in normotensive rats (136 +/- 4 to 113 +/- 8 mmHg, P < 0.01). Additionally, nimesulide decreased GFR (0.9 +/- 0.13 to 0.44 +/- 0.05 ml.min(-1).g(-1), P < 0.05) and RPF (2.79 +/- 0.27 to 1.35 +/- 0.14 ml.min(-1).g(-1), P < 0.05) in hypertensive rats but did not alter GFR or RPF in normotensive rats. Meclofenamate further decreased MAP in hypertensive rats (to 115 +/- 10 mmHg, P < 0.05) but did not decrease MAP in normotensive rats. Meclofenamate did not alter GFR or RPF in either group. These findings demonstrate that COX-1- and COX-2-derived prostanoids contribute importantly to the development of malignant hypertension in Cyp1a1-Ren2 transgenic rats. The data also indicate that COX-2-derived vasodilatory metabolites play an important role in the maintenance of RPF and GFR following induction of malignant hypertension in Cyp1a1-Ren2 transgenic rats.

Factors influencing the development of malignant hypertension in nigeria

Hypertension prevalence rates remain comparatively low in Nigeria, although the associated morbidity and mortality including that due to malignant hypertension (MHT) is considerable. To determine the factors that may be associated with the development of MHT we compared 74 patients with essential MHT (age 48 +/- 9 years, 59 male, blood pressure (BP) 234 +/- 31/140 +/- 17 mm Hg) with 74, age, gender and BP-matched patients with essential benign hypertension (BHT) (49 +/- 8 years, 60 male, 227 +/- 26/136 +/- 15 mm Hg). Body mass index was higher in the BHT group by 1.3 (95% Cl: 0.5 to 2.1, P < 0.01). In the subset (25 MHT, 43 BHT) in whom hypertension had been diagnosed before presentation, duration of hypertension was shorter (P < 0.05) in the MHT group. Patients with MHT, were more likely to have been receiving inadequate therapy in the months before (OR 2.7, 95% Cl: 1.4 to 5.4), showed a decreasing proportion with increasing socio-economic class (chi2 = 5.79, P < 0.02) and had been exposed to a greater degree of stress (OR 3.5, 95% Cl: 1.7 to 7. 1). Smoking (OR 1.1, 0.6 to 2.3), alcohol use (OR 0.9, 0.5 to 1.8) and contraceptive pill use (OR 0.9, 0.1 to 8.6) did not impart excess risk. MHT is associated with the underprivileged and measures aimed at raising the general awareness and the socio-economic level of the people are expected to produce a decline in the incidence of MHT. Journal of Human Hypertension (2000) 14, 171-174.

Factors influencing the development of malignant hypertension in Nigeria.

Hypertension prevalence rates remain comparatively low in Nigeria, although the associated morbidity and mortality including that due to malignant hypertension (MHT) is considerable. To determine the factors that may be associated with the development of MHT we compared 74 patients with essential MHT (age 48 +/- 9 years, 59 male, blood pressure (BP) 234 +/- 31/140 +/- 17 mm Hg) with 74, age, gender and BP-matched patients with essential benign hypertension (BHT) (49 +/- 8 years, 60 male, 227 +/- 26/136 +/- 15 mm Hg). Body mass index was higher in the BHT [corrected] group by 1.3 (95% Cl: 0.5 to 2.1, P < 0.01). In the subset (25 MHT, 43 BHT) in whom hypertension had been diagnosed before presentation, duration of hypertension was shorter (P < 0.05) in the MHT group. Patients with MHT, were more likely to have been receiving inadequate therapy in the months before (OR 2.7, 95% Cl: 1.4 to 5.4), showed a decreasing proportion with increasing socio-economic class (chi2 = 5.79, P < 0.02) and had been exposed to a greater degree of stress (OR 3.5, 95% Cl: 1.7 to 7. 1). Smoking (OR 1.1, 0.6 to 2.3), alcohol use (OR 0.9, 0.5 to 1.8) and contraceptive pill use (OR 0.9, 0.1 to 8.6) did not impart excess risk. MHT is associated with the underprivileged and measures aimed at raising the general awareness and the socio-economic level of the people are expected to produce a decline in the incidence of MHT. Journal of Human Hypertension (2000) 14, 171-174.

Inhibition of tissue angiotensin converting enzyme activity prevents malignant hypertension in TGR(mREN2)27.

Activation of the renin-angiotensin system has been implicated strongly in the transition from benign to malignant hypertension. However, the concomitant rise in blood pressure might also have a direct effect on the vascular wall by initiating fibrinoid necrosis and myointimal proliferation. Ascertaining the relative importance of these two factors in this process has proved difficult. TGR(mREN2)27 heterozygotes (HanRen2/Edin- -) have previously been shown to develop malignant hypertension spontaneously and exhibit the characteristic features of human malignant hypertension. Tissue renin-angtiotensin systems have been implicated in the pathogenesis of malignant hypertension. We set out to determine whether inhibition of this system might protect against development of the disease in a rat model. Male TGR(mREN2)27 heterozygotes (n = 24) were given a non-hypotensive dose of the angiotensin converting enzyme inhibitor ramipril (5 microg/kg per day) from 28 to 120 days of age, untreated rats acting as controls (n = 40). The incidences of malignant hypertension were compared. Systolic blood pressure was measured by tail-cuff plethysmography during treatment; tissue and plasma angiotensin converting enzyme levels and renal histological changes were assessed at the end of the treatment period or upon development of malignant hypertension. Sixty-three per cent of control rats and 4% of angiotensin converting enzyme inhibitor-treated rats had developed malignant hypertension by 120 days despite there having been no significant difference in systolic blood pressure throughout the course of treatment. Angiotensin converting enzyme activities in kidney, heart and resistance vessels, though not that in plasma, were significantly lower in the treated rats. The degree of medial wall thickening did not differ between the two groups whereas evidence of tissue injury (e.g. intimal fibrosis, fibrinoid necrosis and nephron injury) was significantly less common among rats in the angiotensin converting enzyme inhibitor-treated group. Tissue angiotensin converting enzyme inhibition at a non-hypotensive dose almost completely prevented mortality from malignant hypertension and significantly reduced tissue injury in this model, implicating angiotensin II rather than high blood pressure as the principal 'vasculotoxic' agent in malignant hypertension.

Are vasopressin peripheral V1 receptors involved in the development of malignant hypertension and stroke in SHR-SPs?

The aim of this study was to determine whether activation of vasopressin (AVP) peripheral V1 receptors is involved in the development of malignant hypertension, stroke, and end-organ damage in stroke-prone spontaneously hypertensive rats (SHR-SPs). For this purpose, young salt-loaded SHR-SPs were treated orally daily from their 5th to 34th week of age, by a selective AVP V1 receptor antagonist, SR 49059, used in a dose (30 mg/kg) that achieved complete peripheral V1 receptor blockade. Untreated SHR-SPs served as controls. SR 49059 slightly and transiently (8th to 10th week of age) limited the rise in blood pressure, but thereafter systolic blood pressure values were similar in the two groups of SHR-SPs. Stroke-related mortality was not significantly different in SR 49059-treated and in control animals (65% vs 65% at 30 weeks, 65% vs 83% at 34 weeks). SR 49059 did not prevent the increases in fluid intake, diuresis and proteinuria seen in controls. Histological examination of the brain, kidneys and heart revealed that the development of fibrinoid necrosis and arterial thickening was not prevented by SR 49059, nor was that of malignant nephroangiosclerosis and of myocardial infarction and fibrosis. These data strongly suggest that AVP peripheral V1 receptor activation is not involved in the pathological processes that develop in SHR-SPs.

Sequential changes in urinary catecholamine in the transition from benign to malignant hypertension in rats.

The sequential changes in 24-hour urinary norepinephrine (NE) and epinephrine (E) excretion levels were measured in spontaneously hypertensive rats (SHR) that received deoxycorticosterone acetate (DOCA) and 1% NaCl drinking water. These were compared with those from control SHR and similarly treated Wistar-Kyoto rats (WKY). Blood pressure, NE and E increased progressively in DOCA-SHR group, and NE (2392 +/- 94 vs. 998 +/- 49 ng/day) and E (250 +/- 21 vs. 116 +/- 6 ng/day) exceeded twice that of the control SHR group in the sixth week of DOCA treatment. In WKY rats, NE (1372 +/- 48 vs. 968 +/- 37 ng/day) and E (147 +/- 9 vs. 121 +/- 7 ng/day) levels were significantly higher in rats given DOCA than those in control group in the sixth week of the treatment, but were not so remarkably high as in DOCA-SHR group. A histological examination of DOCA-SHR kidneys revealed fibrinoid necrosis in the vascular walls. These data suggest that sympathoadrenal activity plays an important role in the development of malignant hypertension in DOCA-SHR group.

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.

Prevention and Reversal of Malignant Hypertension in Dahl S Rats by Nifedipine

1. Addition of nifedipine to a high salt diet prevented the development of malignant hypertension in the Dahl salt-sensitive strain (Brookhaven) of rats (DS rats). 2. In DS rats with a pre-existent malignant hypertension nifedipine normalized blood pressure, which then correlated with a lower incidence and degree of vasculopathy. 3. Nifedipine appeared to counteract the effect of a supposed humoral pressor agent in DS rats.

Resolution of renal failure with malignant hypertension in scleroderma: Case report and review of the literature

The ominous prognosis of rapidly progressive renal failure associated with malignant hypertension in scleroderma has led to aggressive management by dialysis, early bilateral nephrectomy and renal transplantation. We describe a woman with scleroderma who recovered after the development of malignant hypertension and renal failure. Renal biopsy and arteriography demonstrated the classic vascular lesions of scleroderma with secondary cortical ischemia. Of note, plasma renin activity was normal. Review of the literature revealed 40 patients with scleroderma and rapidly progressive renal failure who have been treated by dialysis. Thirteen patients survived, four of whom did not undergo bilateral nephrectomy. In eight patients treated by transplantation, five achieved excellent allograft function although one sustained a late rejection. Analysis of our case and of five recently reported cases of reversible renal failure and malignant hypertension reveals no distinctive features identifying patients with a favorable prognosis, except for the normal plasma renin activity level in our patient. Vigorous control of hypertension and renal failure by drugs and dialysis is recommended. Bilateral nephrectomy should be considered only for patients with refractory hypertension, since recovery of renal function may follow even after months of dialysis. For patients with irreversible renal failure without other major organ system involvement, transplantation is a reasonable alternative to dialysis.

Renin-angiotensin system in stroke-prone spontaneously hypertensive rats

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.

Development of malignant hypertension as a result of negative sodium balance

Development of malignant hypertension as a result of negative sodium balance

Malignant hypertension: effect of therapy on renin and aldosterone.

Plasma renin activity (PRA) and aldosterone secretion rate (ASR) were measured in 22 patients in balance on a 100 mEq sodium diet during the malignant phase of hypertension and at intervals during long-term follow-up on pharmacological therapy. Three patients had normal PRA and ASR during malignant hypertension. Eighty-six per cent of patients had an increased ASR, but only in 36% was PRA concomitantly increased during malignant hypertension (one patient developed elevated PRA in the postmalignant period). PRA fell to normal in 87% of patients after antihypertensive therapy. ASR fell to normal on drug therapy in six patients, and in all of these there was a period during the postmalignant phase in which ASR was increased while PRA was normal or suppressed. In addition to this group with reversible hyperaldosteronism, all but two of the remaining patients with elevated ASR had periods during which ASR was increased at the same time that PRA was normal or suppressed. These data raise the possibility that either a nonrenin aldosterone-stimulating hormone is secreted in malignant hypertension or that excessive stimulation of the adrenal by angiotensin can lead to persistent hyperfunction of aldosterone-secreting cells with a quantitatively deranged feedback control. One patient had an aldosterone-secreting adenoma and had manifestations of the hyperaldosteronism antedating the development of malignant hypertension.

Malignant Hypertension: Effect of Therapy on Renin and Aldosterone

Plasma renin activity (PRA) and aldosterone secretion rate (ASR) were measured in 22 patients in balance on a 100 mEq sodium diet during the malignant phase of hypertension and at intervals during long-term follow-up on pharmacological therapy. Three patients had normal PRA and ASR during malignant hypertension. Eighty-six per cent of patients had an increased ASR, but only in 36% was PRA concomitantly increased during malignant hypertension (one patient developed elevated PRA in the postmalignant period). PRA fell to normal in 87% of patients after antihypertensive therapy. ASR fell to normal on drug therapy in six patients, and in all of these there was a period during the postmalignant phase in which ASR was increased while PRA was normal or suppressed. In addition to this group with reversible hyperaldosteronism, all but two of the remaining patients with elevated ASR had periods during which ASR was increased at the same time that PRA was normal or suppressed. These data raise the possibility that either a nonrenin aldosterone-stimulating hormone is secreted in malignant hypertension or that excessive stimulation of the adrenal by angiotensin can lead to persistent hyperfunction of aldosterone-secreting cells with a quantitatively deranged feedback control. One patient had an aldosterone-secreting adenoma and had manifestations of the hyperaldosteronism antedating the development of malignant hypertension.