The Protective Effect of the Asystasia chelonoides Extracts on Hypertensive Nephropathy Rats.

BACKGROUND: Hypertensive nephropathy (HN) is one kind of kidney disorders caused by long-term uncontrolled hypertension, usually resulting in severe kidney damage, including inflammation and oxidative stress, no matter in cells or tissues, from patients with nephropathy. In recent years, nephropathy accompanied by hypertension is becoming one of the main causes for kidney replacement therapy, but few effective treatments have been reported for HN treatment. Asystasia chelonoides (AC) is a kind of plant with the effects of anti-inflammation, lowering blood pressure, and anti-oxidative stress. Still, the therapeutic effect of AC in HN rats is not clear. METHODS: To establish HN model by feeding high sugar and high fat diet spontaneously hypertensive rats. Blood measurement, HE staining, PAS staining and biochemical analysis and were used to assess the therapeutic effects of AC extracts and western blotting analyzed the underlying mechanisms of AC extracts treatment in the HN rat model. RESULTS: AC extracts could significantly lower systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) in HN rats; and reduce the expression of total protein (TP), blood urea nitrogen (BUN), microalbuminuria (MALB), creatinine (Cr), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein-cholesterol (LDL-C) concentrations, and also could down-regulate expression of IL-6, MDA and AGEs, up-regulate the expression of SOD in HN rats; HE staining and PAS staining demonstrated that AC extracts could alleviate the histopathological changes in HN rats; western blotting demonstrated that AC extracts could up-regulate the expression of PPARγ and down-regulate the expression of TGFß1 and NF-кB in HN rats. CONCLUSION: The finding of the article demonstrated that AC extracts had the better therapeutic effect for HN, and provided the pharmacological evidences for AC extracts treatment for HN.

Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease.

Dialysis-treated end-stage kidney disease in Libya: epidemiology and risk factors.

PURPOSE: End-stage kidney disease (ESKD) is now a worldwide pandemic. In concert with this, ESKD in Libya has also increased exponentially in recent decades. This review aims to define the magnitude of and risks for this ESKD epidemic among Libyans as there is a dearth of published data on this subject. METHODS: A systematic review was conducted by searching PubMed, EMBASE and Google scholar databases to identify all relevant papers published in English from 2003 to 2012, using the following keywords: end stage, terminal, chronic, renal, kidney, risk factors, Arab, North Africa and Libya. RESULTS: In 2003, the reported incidence of ESKD and prevalence of dialysis-treated ESKD in Libya were the same at 200 per million population (pmp). In 2007, the prevalence of dialysis-treated ESKD was 350 pmp, but the true incidence of ESKD was not available. The most recent published WHO data in 2012 showed the incidence of dialysis-treated ESKD had risen to 282 pmp and the prevalence of dialysis-treated ESKD had reached 624 pmp. The leading causes of ESKD were diabetic kidney disease (26.5 %), chronic glomerulonephritis (21.1 %), hypertensive nephropathy (14.6 %) and congenital/hereditary disease (12.3 %). The total number of dialysis centers was 40 with 61 nephrologists. Nephrologist/internist to patient ratio was 1:40, and nurse to patient ratio was 1:3.7. Only 135 living-related kidney transplants had been performed between 2004 and 2007. There were no published data on most macroeconomic and renal service factors. CONCLUSIONS: ESKD is a major public health problem in Libya with diabetic kidney disease and chronic glomerulonephritis being the leading causes. The most frequent co-morbidities were hypertension, obesity and the metabolic syndrome. In addition to provision of RRT, preventive strategies are also urgently needed for a holistic integrated renal care system.

[Effects of Xinjierkang on two kidney one clip-induced hypertension and target organ injury in rats].

OBJECTIVE: To investigate the effects of Xinjierkang on two kidney one clip -induced hypertension and target organ injury in rats. METHODS: Two kidney one clip-induced hypertension rats model was established. Rats were divided into control group, model group, Xinjierkang group, and fosinopril group. At the end of 8th w, the hemodynamics indexes were recorded. The cardiac hypertrophy index was expressed as heart weight/body weight (HW/BW), the histological changes of heart, aorta and kidney were investigated by HE and/or Van Gieson stain. RESULTS: Compared with control group, the heart systolic and diastolic function were impaired, the heart weight index, cardiomyocytes cross section area (CSA), cardiac collagen deposition, vascular remodeling index and glomerulus area were increased markedly in model group rats. Administration of Xinjierkang and fosinopril markedly ameliorated hemodynamic indexes, inhibited the elevation of HW/BW ratio, CSA of cardiomyocytes, vascular remodeling index and glomerulus hypertrophy, decreased collagen deposition in heart. CONCLUSION: Xinjierkang has protective effects against two kidney one clip-induced hemodynamic impairment, cardiovascular remodeling and glomerulus hypertrophy in rats.

[Effect of N-stearoylethanolamine(NSE) on activity of angiotensine-converting enzyme in the brain structures and blood plasma of rats with streptozotocine-induced diabetes].

The influence of saturated N-acylethanolamine--N-stearoylethanolamine (NSE) on the activity of angiotensine-converting enzyme (ACE) in the brain structures of rats with streptozotocine-induced diabetes was studied. It was shown that decreased activity of ACE was observed in the hypothalamus, increased--in the anterior pituitary. The NSE suspension administration to rats with experimental diabetes in a dose 50 mg/kg of body weight during 10 days caused a decrease in ACE activity in the anterior pituitary, whereas in the hypothalamus and hippocampus ACE activity did not change significantly. At the same time, introduction of NSE to intact animals led to the reduction of activity of ACE in the hippocampus, anterior pituitary and blood plasma. It is known that the highest amount of ACE in the brain structures is located in the membrane-bound state. Thus, the changes we have found in the activity of ACE in the control rats and in animals with induced diabetes may be related to the ability of NSE to the modulation of cell membranes lipid profile. Changes in the activity of ACE under the action of N-acylethanolamines may be one of the mechanisms for implementation of anti-hypertensive and anti-inflammatory action of these compounds.

[Effect of Cornus officinalis fruit core extract on the cardiac hypertrophy induced by two kidney two clip].

OBJECTIVE: To observe the effect of Cornus officinalis fruit core extract on cardiac hypertrophy induced by two kidney two clip (2K2C) and its mechanism. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups: sham-operated group, model group and treatment groups (300, 600 mg/kg). Rats were intragastric administered medicine for 4 weeks from the fourth week after surgery. Sham-operated and 2K2C rats were given vehicle for 4 weeks. Blood pressure and hemodynamic parameters were measured. Left ventricular weight to body weight (LVM/BM) ratio was calculated. Paraffin-embedded hearts were cut into 5 microm slices, which were stained with hematoxylin-eosin (HE) and Masson for morphological analysis; Western-blot analysis was performed to investigate the effects of Cornus officinalis fruit core extract on the expression of P47phox, Nox4 in myocardium. RESULTS: Compared with sham-operated group, the blood pressure and LVM/BM ratios were markedly elevated in model groups. Meanwhile cardiomyocyte cross sectional areas was markedly increased and myocardial fibers showed disordered arrangement while these parameters were markedly reversed after treatment with Cornus officinalis fruit core extract for 4 weeks. At 8th weeks after operation, model rats developed obvious LV hypertrophy. Cornus officinalis fruit core extract, more significant in high dose, decreased the blood pressure and LVM/BM ratios and reversed the cardiomyocyte hypertrophy and myocardial fibrosis. Moreover, Cornus officinalis fruit core extract decreased the expression of P47phox and Nox4 which elevated in LV in model rats. CONCLUSION: Cornus officinalis fruit core extract could significantly decrease the blood pressure, reverse cardiac hypertrophy and improve the function of heart which is possibly associated with the down-regulation of P47phox and Nox4.

Transient nitric oxide reduction induces permanent cardiac systolic dysfunction and worsens kidney damage in rats with chronic kidney disease.

Left ventricular systolic dysfunction (LVSD) in patients with chronic kidney disease (CKD) is associated with poorer prognosis. Because patients with CKD often exhibit progressively decreased nitric oxide (NO) availability and inhibition of NO production can reduce cardiac output, we hypothesized that loss of NO availability in CKD contributes to pathogenesis of LVSD. Subtotally nephrectomized (SNX) rats were treated with a low dose of the NO synthase inhibitor N(omega)-nitro-L-arginine (L-NNA; 20 mg/l water; SNX+L-NNA) and compared with relevant control groups. To study permanent changes separate from hemodynamic effects, L-NNA was stopped after week 8 and rats were followed up to week 15, until blood pressure was similar in SNX+L-NNA and SNX groups. To study effects of NO depletion alone, a control group with high-dose L-NNA (L-NNA-High: 100 mg/l) was included. Mild systolic dysfunction developed at week 13 after SNX. In SNX+L-NNA, systolic function decreased by almost 50% already from week 4 onward, together with markedly reduced whole body NO production and high mortality. In L-NNA-High, LVSD was not as severe as in SNX+L-NNA, and renal function was not affected. Both LVSD and NO depletion were reversible in L-NNA-High after L-NNA was stopped, but both were persistently low in SNX+L-NNA. Proteinuria increased compared with rats with SNX, and glomerulosclerosis and cardiac fibrosis were worsened. We conclude that SNX+L-NNA induced accelerated and permanent LVSD that was functionally and structurally different from CKD or NO depletion alone. Availability of NO appears to play a pivotal role in maintaining cardiac function in CKD.

Ebselen attenuates oxidative DNA damage and enhances its repair activity in the thalamus after focal cortical infarction in hypertensive rats.

Oxidative DNA damage has been proposed to be a major contributor to focal cerebral ischemic injury. However, little is known about the role of oxidative DNA damage in remote damage secondary to the primary infarction. In the present study, we investigated oxidative damage within the ventroposterior nucleus (VPN) after distal middle cerebral artery occlusion (MCAO) in hypertensive rats. We also examined the possible protective effect of ebselen, one glutathione peroxidase mimic, on delayed degeneration in the VPN after distal MCAO. Neuronal damage in the ipsilateral VPN was examined by Nissl staining. Oxidative DNA damage and base repair enzyme activity were assessed by analyzing immunoreactivity of 8-hydroxy-2'-deoxyguanosine (8-ohdG) and 8-oxoguanine DNA glycosylase (OGG1), respectively. The number of intact neurons in the ipsilateral VPN decreased by 52% compared to the contralateral side in ischemia group 2 weeks after distal cerebral cortical infarction. The immunoreactivity of 8-ohdG significantly increased while OGG1 immunoreactivity significantly decreased in the ipsilateral VPN 2 weeks after distal cortical infarction (all p<0.01). Compared with vehicle treatment, ebselen significantly attenuated the neuron loss, ameliorated ischemia-induced increase in 8-ohdG level as well as decrease in OGG1 level within the ipsilateral VPN (all p<0.01). OGG1 was further demonstrated to mainly express in neurons. These findings strongly suggest that oxidative DNA damage may be involved in the delayed neuronal death in the VPN region following distal MCAO. Furthermore, ebselen protects against the delayed damage in the VPN when given at 24 h following distal MCAO.

Cardiovascular reactivity in patients with essential or renal hypertension under standardized mental stress.

Introduction. Patients with essential hypertension react more strongly to mental stress than normotensives. This may be related to the type of stress coping or to increased reactivity associated with the disease. The aim of our study was to examine whether patients with essential or secondary hypertension differ in their reaction to mental stress. Methods. Seventeen patients with essential hypertension (EH), 9 patients with renal hypertension (RH), and 22 normotensive controls (N) with no circulatory disorders were subjected to a psychophysiological examination under mental stress. Blood pressure (BP), heart rate (HR) and electrodermal activity (EDA) were measured. Results. The two hypertensive groups differed in their BP reaction to mental stress from the control group but not from each other. The product of heart rate and systolic blood pressure during the matrix test was significantly higher in essential than renal hypertensives (EH median: 13344; RH median: 12154.5; p = 0.04). This also holds true for the number of spontaneous fluctuations of EDA in the resting phase after the experiment (EH. median: 3.2; RH. median: 1.3; p = 0.01). Conclusion. The results suggest that not only a high blood pressure level but also the sympathetic nervous tone are responsible for the blood pressure response to mental stress. Due to very different (perhaps psychosocially triggered) conditions, essential hypertension leads to a stronger cardiovascular reaction under mental stress than renal hypertension.

Circadian blood pressure variation and antihypertensive medication adjustment in normoalbuminuric type 2 diabetes patients.

BACKGROUND/AIMS: The aim of the study was to assess the effect of an antihypertensive treatment adjustment on 24-hour blood pressure variation in type 2 diabetes patients. METHODS: The study group included 59 hypertensive type 2 diabetes patients subjected to a single one-step antihypertensive agent dose adjustment (increase or decrease). Ambulatory blood pressure monitoring was performed at baseline and 4-6 weeks after the treatment modification. Controls were 41 matched patients, in whom antihypertensive treatment remained unchanged. RESULTS: At baseline, 45 (76%) study group patients and 29 (71%) controls were 'non-dippers'; a similar number of patients in both groups converted to 'dipping' or vice versa: 11 (19%) from the study group and 7 (17%) controls. 'Converters' from the study group were significantly younger (47.5 +/- 3.9 vs. 56.4 +/- 12.2 years; p < 0.05) and had lower 24-hour systolic blood pressure than 'non-converters': 113.7 +/- 7.2 vs. 127.7 +/- 20.3 mm Hg (p < 0.01). CONCLUSION: A single one-step antihypertensive medication adjustment does not affect 'dipping' status in type 2 diabetes patients. However, the assessment of blood pressure variation should be made with greater caution in younger type 2 diabetes subjects with low systolic blood pressure.

Managing Henoch-Schonlein purpura in children with fish oil and ACE inhibitor therapy.

BACKGROUND: Henoch-Schonlein purpura (HSP) is a vasculitic syndrome with palpable purpura and renal involvement. The treatment for HSP with persistent renal disease remains controversial. The kidney biopsy in HSP shows IgA deposits and fish-oil therapy has proven to be promising in halting the progression of IgA nephropathy. METHODS: Five children with biopsy-proven HSP with repeated episodes of haematuria and proteinuria were treated with fish oil (1 g orally twice daily). In three of the five patients an angiotensin-converting enzyme inhibitor (ACEI) was added for hypertension. RESULTS: The mean duration of follow up after starting fish-oil therapy was 49.2 weeks. The protein excretion rate prior to starting fish oil was 1041 mg/day and on the last follow-up visit the rate had decreased to 104 mg/day (P <0.05). The average blood pressure (BP) prior to therapy was 135/82. On the last follow-up visit the average BP off ACEI had decreased to 100/54 (P <0.05). After a year of follow up serum creatinine and glomerular filtration rates have remained stable at 51.2 micromol/L and 128 mL/min/1.73 m2, respectively. CONCLUSION: This is the first report of abatement of HSP with fish oil and ACEI in children. There is a need for randomized prospective trials to confirm this observation.

Supplementation with a low dose of L-arginine reduces blood pressure and endothelin-1 production in hypertensive uraemic rats.

BACKGROUND: We documented recently that increased endothelin-1 (ET-1) production in blood vessels and glomeruli of uraemic rats plays a crucial role in the development of hypertension and the progression of chronic renal failure. Normally, biological effects and local production of ET-1 are attenuated by the immediate release of nitric oxide (NO). Increasing evidence suggest, however, that NO release is impaired in chronic renal failure. We investigated whether supplementation with L-arginine, the natural precursor of NO, improves NO synthesis in uraemic rats with reduced renal mass and modulates vascular and renal ET-1 production as well as blood pressure and renal failure progression. METHODS: One week after surgical renal mass reduction, the uraemic and sham-operated animals received either no treatment or 0.1% L-arginine in drinking water for 5 weeks. In another series of experiments, uraemic rats received 1% L-arginine for 5 weeks. Immunoreactive-ET-1 (ir-ET-1) levels in plasma, urine, and vascular and renal tissue preparations was measured by radioimmunoassay after sample extraction and purification. RESULTS: Before treatment, systolic blood pressure was significantly elevated in uraemic animals compared to sham-operated controls (156+/-7 vs 111+/-3 mmHg, respectively; P<0.01). Thereafter, systolic blood pressure increased further in uraemic-untreated rats (systolic blood pressure at week 5; 199+/-9 mmHg, P<0.01), whereas it remained similar in uraemic rats supplemented with 0.1% L-arginine (171+/-9 mmHg, NS). At the end of the study, serum creatinine and urea, proteinuria and ir-ET-1 excretion were significantly augmented, while creatinine clearance was reduced in uraemic animals compared to the controls. Ir-ET-1 level was also increased in glomeruli as well as in thoracic aorta, mesenteric arterial bed, and pre-glomerular arteries, and was associated with vascular hypertrophy as assessed by tissue weight. In contrast, ir-ET-1 level was diminished in the renal papilla of uraemic rats. Treatment with 0.1% L-arginine significantly reduced proteinuria and urinary ir-ET-1 excretion (P<0.05) as well as ir-ET-1 level in glomeruli (P<0.01) and in thoracic aorta (P<0.05). These changes were associated with increased plasma NO metabolites NO2/NO3 levels in L-arginine-treated animals (P<0.01) and reduced aortic hypertrophy (P<0.05). In contrast, supplementation with 1% L-arginine had no effect on systolic blood pressure in uraemic rats, but exacerbated proteinuria and urinary ir-ET-1 excretion and increased serum urea (P<0.05) were observed. CONCLUSIONS: These results indicate that improvement of NO release with a low dose but not with a high dose of L-arginine significantly attenuates the development of hypertension and the progression of renal insufficiency in rats with reduced renal mass. These protective effects may be mediated in part by the reduction of vascular and renal ET-1 production.

Genetic differences define severity of renal damage after L-NAME-induced hypertension in rats.

Genetic factors are important in determining the susceptibility to renal damage. In a backcross of the hypertensive and proteinuric fawn-hooded Erasmus University Rotterdam (FHH/EUR) rat with the normotensive, nonproteinuric August Copenhagen Irish (ACI/EUR) rat, two genes (denoted Rf-1 and Rf-2) were genetically mapped for parameters of functional and structural renal damage. The aim of the present study was to investigate the susceptibility to functional and structural renal damage in heterozygous (FHH X ACI) F1 rats compared with the parental FHH and ACI strains at similar levels of systolic BP (SBP). BP elevation was induced by chronic treatment with NG-nitro-L-arginine methyl ester (L-NAME) in either a low dose (LD, 75 to 100 mg/L) or a high dose (HD, 175 to 250 mg/L) in the drinking fluid. Survival of FHH rats and, to a lesser extent, F1 rats, was adversely affected by L-NAME treatment. All ACI rats except for one ACI-HD animal survived. In all strains, L-NAME caused a dose-dependent increase in SBP. At similar levels of SBP, the increase in functional renal damage, as indicated by the level of albuminuria, was higher in F1 compared with ACI, but lower compared with FHH. The same differences were found for the level of structural renal damage, as indicated by the incidence of glomerulosclerosis. Both the SBP and the average BP burden (SBP-Av), defined as SBP averaged over the period of follow-up, directly correlated with the level of albuminuria and incidence of glomerulosclerosis in all strains. However, the increase in the degree of renal damage per mmHg increase in SBP or SBP-Av was significantly higher in the F1 rats compared with ACI, but lower compared with FHH rats. Values for these F1 rats were closer to the ACI rats than to values for the FHH rats and increased above an SBP level of 180 mmHg. The F1 rats, being heterozygous for Rf-1 and Rf-2, as well as for other potential genes responsible for renal disease, were largely, but not completely, protected from hypertension-induced renal damage. It is concluded that complete susceptibility to hypertension-associated renal damage in rats primarily depends on the presence of predisposing genes for renal failure even after a significant increase in BP.

Deterioration rate in hypertensive IgA nephropathy: comparison of a converting enzyme inhibitor and beta-blocking agents.

The effect of beta-blocking agents and enalapril as antihypertensive drugs has been compared in 47 patients with IgA nephropathy. The deterioration rate was calculated from the regression line of 51Cr-EDTA clearance and expressed in ml/min/year. The annual loss in glomerular filtration rate (GFR) was greater in patients treated with different beta-blocking agents (-4.9 +/- 6.8 ml/min/year) compared to patients treated with Enalapril (1.7 +/- 7.4 ml/min/year), in spite of the fact that these patients had a lower initial GFR. Nine patients were initially treated with beta-blocking agents (-9.5 +/- 9.3 ml/min/year) and then with an angiotensin-converting enzyme inhibitor (5.5 +/- 11.2 ml/min/year). Angiotensin-converting enzyme inhibitors should therefore be preferred in the treatment of hypertension in IgA nephropathy.

Calcium channel blocker nisoldipine in chronic renal failure.

Patients with a stable progression of chronic renal failure with a creatinine clearance of 15-45 mL/min were randomly assigned to two groups of antihypertensive therapy: 1--nisoldipine as the only antihypertensive agent and 2--antihypertensive drugs without calcium channel blockers and a placebo tablet instead of nisoldipine. The patients were already on a low-protein diet and some form of antihypertensive therapy but without calcium channel blockers. There were 18 patients in the placebo group and 20 patients in the nisoldipine group. The follow-up period averaged 23.7 +/- 10.6 (SD) months in the placebo group and 23 +/- 11.3 months in the nisoldipine group. The slopes of the reciprocal of serum creatinine were calculated for the period prior to and following our intervention. The number of patients whose slopes improved following intervention was 6/18 in the placebo group and 15/20 in the nisoldipine group (p less than .02). The patients whose slopes improved had a significant fall in systolic and diastolic BP, as well as in the MAP. Those whose slopes did not improve had a significant decrease in systolic BP, but no change in diastolic BP and no significant difference in the MAP. When all 38 patients are analyzed together, regardless of their grouping, the correlation between the difference percent in the slope, and the difference percent in the MAP, was significant. Furthermore, punch biopsies of the skin showed a markedly different calcium content in the two groups, which was significantly less in the nisoldipine-treated patients as compared with the patients not receiving calcium blockers.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive effects of nitrendipine and cilazapril alone, and in combination in hypertensive patients with chronic renal failure.

1. It has been reported that calcium antagonists lower blood pressure more effectively in salt replete hypertensive patients with a low plasma renin activity (PRA), whereas angiotensin converting enzyme (ACE) inhibitors are more effective in salt depleted patients with a high level of PRA. An inverse relationship between the antihypertensive effects of these two groups of drugs might therefore be expected. 2. Since salt retention and inappropriately high levels of PRA are said to contribute to hypertension in patients with chronic renal failure (CRF), an additive antihypertensive effect with both drugs might also be expected in such patients. 3. To test these hypotheses, we investigated the acute and chronic antihypertensive effects of the calcium antagonist nitrendipine and the new ACE inhibitor cilazapril, given alone, and in combination, in a double-blind, randomized, placebo controlled study of 11 hypertensive patients with chronic renal failure who had a mean pretreatment blood pressure of 149 +/- 3/96 +/- 2 mm Hg. Patients received nitrendipine 10 mg, cilazapril 1.25 or 2.5 mg depending on creatinine clearance, or placebo once daily orally. Nitrendipine and cilazapril were also combined at the same doses. 4. Nitrendipine and cilazapril were equally effective, with a maximal acute reduction of mean arterial pressure (MAP) of 5.3 +/- 1.8% and 8.0 +/- 1.9%, and after 1 week of treatment 5.0 +/- 2.4% and 8.1 +/- 1.8%, respectively. In individual patients no inverse relationship between the blood pressure responses to the two drugs was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive drug therapy prevents cerebral microvascular abnormalities in hypertensive rats.

Studies were performed on anesthetized 16-18 week old normotensive Wistar-Kyoto rats, spontaneously hypertensive rats, and Goldblatt two-kidney one clip renal hypertensive rats, treated from age 4-5 weeks with an oral antihypertensive regimen consisting of hydralazine, reserpine, and chlorothiazide. Measurements of flow and intravascular pressure in the cerebral microvasculature were made via a constantly suffused open cranial window using video microscopy. A significant upward shift was seen in the pressure range for cerebral blood flow autoregulation in both groups of untreated hypertensive animals. Following treatment, the autoregulatory range in both hypertensive models was restored to a level nearly identical to control. The prevention of this shift in treated animals was due primarily to the prevention of structural microvascular adaptations that occur in untreated hypertensive animals. By preventing elevations in microvascular pressure, treatment may have eliminated the major stimulus for development of hypertrophy in resistance vessels. However, a persistent increment of arteriolar wall mass in treated spontaneously hypertensive rats may represent a hyperplastic response not influenced by treatment. Likewise, a persistent constriction of the smallest arterioles in treated renal hypertensive rats may represent a differential sensitivity of microvessels to circulating vasoactive agents. It appears that treatment initiated in the prehypertensive state, or before significant sustained hypertension has occurred, can markedly reduce the cerebrovascular morbidity associated with two different forms of hypertension.

Use of prazosin in management of hypertension in patients with chronic renal failure and in renal transplant recipients.

Prazosin was used in combination with other antihypertensive drugs in the successful management of hypertension in seven patients with chronic renal failure and six renal transplant recipients, also with chronic renal failure. The addition of small doses of prazosin (mean 3 mg/day) to the antihypertensive regimen produced significant falls in systolic and diastolic blood pressures in both the lying and standing positions. The standing blood pressures were significantly lower than the lying blood pressures during prazosin treatment. Neither the mean blood urea concentrations nor the mean plasma creatinine concentrations changed significantly during prazosin administration. Chromium-51 edetic acid clearances did not change significantly during prazosin treatment in the seven patients in whom it was measured. Severe symptomatic postural hypotension occurred in one patient a week after starting prazosin 3 mg/day. This hypotensive episode was associated with a transient and reversible deterioration in renal function. Another patient developed a rash while on prazosin but it was probably related to propranolol rather than prazosin. Prazosin is thus an effective antihypertensive drug in patients with chronic renal failure, and it may be used with a variety of other drugs. It should be used cautiously, however, since patients with chronic renal failure may respond to small doses, and significant postural falls in blood pressure may result. There was no evidence that the use of prazosin resulted in progressive deterioration in the residual renal function of the patients with chronic renal failure.