Angiotensin-converting enzyme (ACE) insertion/deletion polymorphism and survival in a cohort of chronic hemodialysis patients.

BACKGROUND: There are conflicting reports regarding the relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and the initiation and progression of cardiovascular disease. Moreover, there is no report regarding the relationship between the ACE I/D polymorphism and the prognosis of chronic dialysis patients. METHODS: We examined the frequency of the ACE I/D polymorphism in 727 chronic hemodialysis patients in Okinawa, Japan, and observed the prognosis over 2 years in 407 men and 320 women with mean age (SD) of 55.5 (13.9) years with a mean duration of dialysis of 84.3 (66.6) months. RESULTS: Genotype frequencies were 42.1% for II, 43.2% for ID, and 14.7% for DD. The relative risks of death were examined by Cox-proportional hazards analysis after adjusting for age, sex, age at the start of dialysis, presence of diabetes mellitus and hypertension and total cholesterol and serum albumin levels. The adjusted hazard ratio (95% confidence interval) was 1.03 (0.38 - 2.85) for DD genotype and 1.50 (0.83 - 2.70) for DD+ID genotype when compared to II genotype. CONCLUSION: ACE I/D polymorphism appears to have no relation to the short-term prognosis in chronic hemodialysis patients.

Evidence for high incidence of end-stage renal disease in patients after stroke and acute myocardial infarction at age 60 or younger.

The impact of stroke and acute myocardial infarction (AMI) on the incidence of end-stage renal disease (ESRD) is unknown. Two community-based registries, one of patients with stroke or AMI and another of patients with ESRD who undergo dialysis, are available in Okinawa, Japan. Whether survivors after stroke and AMI who were registered from April 1988 through March 1991 entered an ESRD dialysis program by the end of December 1999 was determined. Among 4,556 patients (3,809 patients with stroke, 747 patients with AMI) who survived at least 28 days after the event onset, 44 patients (36 patients, stroke; 8 patients, AMI) entered an ESRD dialysis program during the study period. The 10-year cumulative incidence of ESRD was approximately 2.0% in those who survived stroke or AMI. The observed-expected ratio was 4.1 in men (P < 0.01) and 5.8 in women (P < 0.01) aged 30 to 59 years and 0.8 in men (not significant) and 0.4 in women (not significant) 60 years and older. The present results confirm that survivors after stroke or AMI have a greater incidence of ESRD than those in the general population, in particular, those who had stroke or AMI at 60 years or younger.

High heart rate relates to clustering of cardiovascular risk factors in a screened cohort.

Increased heart rate (HR) is a predictor of cardiovascular mortality, so the present study used a screened cohort to investigate whether the clustering of cardiovascular risk factors is associated with increased HR. Individuals who were receiving medication for hypertension or heart disease and those who did not have an ECG record or who had a record of arrhythmia were excluded. In total, 8,508 subjects (5,299 men, 3,209 women; age range, 18-89 years) were studied. Subjects were divided into 2 HR classes using the value of mean HR+ 1 SD as the cut-off point: low HR (HR < 77 beats/min, n=7,320) and high HR (HR > or = 77 beats/min, n=1,188). For logistic regression analysis, the dependent variable was HR class and the independent variables were the number of risk factors (ie, hypertension, diabetes mellitus, and hypertriglyceridemia each of which was associated positively with HR class by multivariate analysis). The odds ratios and 95% confidence intervals for the number of risk factors were 1.412 (1.216-1.640) for 1 risk factor, 2.800 (2.269-3.455) for 2, and 4.582 (2.815-7.459) for 3. Multivariate regression analyses showed that the number of risk factors from 0 to 3 correlated positively with high HR. HR increased significantly with clustering of risk factors even with low HR (regression coefficient was 1.147, p<0.0001). Modifying the risk factors may lower HR and reduce cardiovascular mortality.

Family history of hypertension and blood pressure in a screened cohort.

We sought to determine whether a family history of hypertension is quantitatively associated with the prevalence of hypertension and blood pressure in a screened cohort. Clinical data and family (parents and siblings) histories regarding hypertension were collected from 9,914 individuals (probands) who were interviewed and examined during a one-day clinic by the Okinawa General Health Maintenance Association in 1997. We used logistic analysis to calculate odds ratios with adjustments for age, sex, body mass index, total cholesterol, presence of diabetes mellitus, alcohol use, cigarette smoking, and status of physical exercise. The age- and sex-adjusted hypertension prevalences in probands were 29.0% for those with 1 family member with a history of hypertension (n=2,112), 37.6% for those with 2 hypertensive family members (n=374), and 47.3% for those with 3 or more hypertensive family members (n=68). In contrast, only 16.4% of probands who reported no family history of hypertension (n=7,360) were hypertensive themselves. The trend of the prevalence according to the number of family members with a history of hypertension was significantly positive (p=0.003). The adjusted odds ratios (95% confidence interval) of hypertension were 2.74 (2.43-3.10) for 1 member, 4.62 (3.62-5.90) for 2 members, and 6.04 (3.51-10.4) for 3 or more members with a history of hypertension. In patients without antihypertensive medication (n=9,009), systolic/diastolic blood pressure (mean +/- SD) was 121 +/- 17/75 +/- 11 for 1 member, 124 +/- 18/77 +/- 12 for 2 members, and 127 +/- 17/78 +/- 11 for 3 or more members with a history of hypertension. In contrast, the mean systolic/diastolic blood pressure of probands who reported no family history of hypertension (n=7,360) was 119 +/- 15/74 +/- 10 mmHg, which was significantly (p<0.05) lower than that of any of the groups with hypertensive family members. In conclusion, an increase in the number of family members with hypertension was associated with an increasing prevalence of hypertension and blood pressure in the probands, independent of conventional risk factors for hypertension. Family members of hypertensive subjects may need to be treated in primary prevention efforts related to hypertension.

Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects.

A high level of serum creatinine (S-Cr) is a predictor of end-stage renal disease (ESRD), but only a few studies have investigated the prevalence of high S-Cr and its correlates in a large population. We analyzed the data collected from 6,403 subjects (4,222 men and 2,181 women) who participated in the Okinawa General Health Maintenance Association (OGHMA) screening both at 1997 and 1999. The computer-saved data included sex, age, blood chemistries, blood pressure, medical histories, and lifestyles. Multivariate Cox proportional hazard analyses were performed to identify the correlates of developing high S-Cr levels: > or = 1.4 mg/dl in men and > or = 1.2 mg/dl in women. The prevalence of high S-Cr was 3.0% (N=193), which was 4.1% in men (N=175) and 0.8% in women (N=18), and increased with age in both sexes at the 1997 screening. Among those who showed normal levels of S-Cr in 1997 (N=6,210), 241 subjects (223 men and 18 women) developed high S-Cr. The 2-year cumulative incidence of high S-Cr was 5.5% in men and 0.8% in women. Other than sex, serum uric acid was the most significant correlate for developing high S-Cr. The adjusted relative risk (95% confidence interval) of those with serum uric acid 8.0 mg/dl and over was 2.91 (1.79-4.75) in men and 10.39 (1.91-56.62) in women when compared to those with serum uric acid less than 5.0 mg/dl. Prevalence of high levels of S-Cr was relatively high in men. Other than gender, serum uric acid was a significant positive correlate of developing high S-Cr in this sample of the Japanese population.

Multiple risk factor clustering of hypertension in a screened cohort.

OBJECTIVE: A family history of hypertension, obesity, diabetes mellitus, hypercholesterolaemia and hypertriglyceridaemia have all been associated with the risk for hypertension. We evaluated whether the clustering of these risk factors increases the risk for hypertension or whether the accumulation of risk factors is associated with the blood pressure level in non-hypertensive subjects. METHODS AND SUBJECTS: We assessed the clinical data and family history of hypertension (in parents and siblings) for 9914 individuals (6163 men and 3751 women, 18-89 years old) who were screened in Okinawa, Japan, in 1997. RESULTS: In 9914 subjects (2465 hypertensive and 7449 non-hypertensive subjects), all the five factors were positively associated with hypertension. The odds ratios (95% confidence interval) for the number of risk factors were 1.88 (1.62-2.18) for one risk factor, 3.06 (2.62-3.57) for two, 5.25 (4.37-6.30) for three, 8.71 (6.48-11.72) for four and 24.48 (8.49-70.56) for five, after adjusting for age, sex, alcohol consumption, cigarette smoking and physical exercise habits. In non-hypertensive subjects, multivariate regression analyses showed that the number of risks was positively correlated with blood pressure; the regression coefficient was 1.96 (P < 0.0001) for systolic blood pressure, and 1.47 (P < 0.0001) for diastolic blood pressure after adjusting for age and sex. CONCLUSIONS: Clustering of risk factors was significantly associated with hypertension. The number of risk factors positively correlated with the blood pressure levels in nonhypertensive subjects. The accumulation of risk factors may play an important role in the pathogenesis of hypertension, and thus the aggregation of risk factors may need to be addressed in primary prevention efforts related to hypertension.

Non-corresponding effects of an angiotensin-converting enzyme inhibitor on cardiac and vascular hypertrophy in spontaneously hypertensive rats.

Angiotensin-converting enzyme inhibitors (ACEIs) may have different effects on cardiac hypertrophy than on vascular hypertrophy. Arginine vasopressin (AVP) may promote cardiac hypertrophy. Our aims were (1) to simultaneously examine the chronic effects of ACEIs on hypertrophy of the heart and hypertrophy of the coronary and renal interlobular arteries, and (2) to clarify the relation between AVP concentration (AVPC) and cardiac hypertrophy. ACEI (delapril: 30 mg/kg/day) or vehicle (5% arabic gum) was administered in a preventive (4 to 28 weeks of age) or a therapeutic (12-24 weeks of age) protocol in spontaneously hypertensive rats. In both protocols, delapril produced a slight but significant decrease in systolic blood pressure. In the therapeutic protocol, the weight of the left ventricle (mean+/-SE) was lower (p<0.05) in the ACEI group (64+/-2 mg/100 g body weight) than in the control group (69+/-1 mg/100 g body weight). Plasma renin activity was significantly higher in the ACEI group than in the control group in both the preventive (p <0.01) and therapeutic (p<0.01) protocols. In the therapeutic protocol, AVPC was significantly (p<0.05) lower in the ACEI group than in the control group. AVPC was significantly (p=0.02, r=0.46) correlated with the weight of the left ventricle in the therapeutic protocol. For both protocols, no differences were noted between the ACEI and control groups in the vascular hypertrophy of the coronary and renal interlobular arteries. We conclude that (1) the preventive or therapeutic effect of ACEIs on hypertrophy may not be the same in the heart as in the coronary and renal arteries; and (2) AVP was significantly correlated with the left ventricular weight. This indicates that AVP could play a role in the etiology of cardiac hypertrophy in SHR.

Seasonal blood pressure and body weight variation in patients on chronic hemodialysis.

AIM: The relation of ambient temperature (AMT) and relative humidity to systolic blood pressure (SBP), diastolic blood pressure (DBP), body weight (BW), and body weight gain between dialysis sessions (DeltaBW) was examined in hemodialysis patients by Fourier analysis. METHODS AND RESULTS: The authors recruited 144 dialysis patients from a hemodialysis center in Okinawa, Japan where there is distinct seasonal variation in monthly AMT but a constant intradiurnal temperature change throughout the year. All patients had been undergoing chronic and regular hemodialysis three times per week. SBP, DBP, and BW before dialysis sessions and DeltaBW were recorded in 1994. Mean monthly Okinawa AMT in 1994 was highest in August and lowest in February and March, and the mean monthly relative humidity in 1994 was highest in June and lowest in January. Mean SBP and DBP were lowest in August and June respectively, and greatest in December. BW was lowest in July and September, and greatest in February and March; DeltaBW was lowest in July and greatest in January. These seasonal patterns were well reproduced by the first Fourier component. The cross-correlation coefficient showed that monthly mean AMT and SBP, DBP, BW, and DeltaBW were correlated with a lag time of 5 or 6 months. The cross correlation coefficient showed that relative humidity and SBP, DBP and DeltaBW were also correlated with a 6-month lag time. In analyzing subgroups of patients according to the presence or absence of antihypertensive medications, a seasonal change was observed in the SBP and DBP of patients not being treated with antihypertensives, and in the DBP of patients taking antihypertensive medications, but not in the SBP of patients taking antihypertensive medications. CONCLUSION: Seasonal variations in SBP, DBP, BW and DeltaBW were evident. AMT and the relative humidity correlated strongly with SBP, DBP, BW and DeltaBW. The clinical implications of these findings in hemodialysis patients warrant further investigation.

Serum C-reactive protein (CRP) and risk of death in chronic dialysis patients.

BACKGROUND: The prognosis of chronic dialysis patients is poor, in part due to the high incidence of cardiovascular disease. Malnutrition, such as hypoalbuminaemia, has been shown to be a predictor of death in this group of patients, while serum C-reactive protein (CRP) is a predictor of myocardial infarction and sudden death. Thus, the aim of the present study was to determine of the relationship between CRP and serum albumin concentration, and the value of baseline CRP data in the prediction of death. METHODS: In one of the dialysis units in Okinawa, Japan, baseline CRP data was available (n=163, 95 men and 68 women) in January 1991. These patients were divided into two groups according to their baseline CRP levels, with group 1 consisting of CRP<10 mg/l (n=128) and group 2 of CRP> or =10 mg/l (n=35), and then followed up until the end of 1997. Survival curves were calculated using the Kaplan-Meier method. The statistical significance of the relationship between CRP levels and the risk of death was evaluated by multiple logistic analysis with covariables such as age, sex, diabetes mellitus, serum albumin, and blood pressure. RESULTS: The mean (SD) level of serum albumin was 38 (3) g/l in group 1 and 36 (3) g/l in group 2 (P<0.00001). The 5-year survival rate was significantly poorer in group 2 (44.4%) than in group 1 (82.5%) (P<0.0001). Furthermore, the risk of death was significantly higher in group 2 (relative risk 3.48 (95% confidence interval 1.76-6.89), P<0.0003) by multivariate Cox proportional hazard analysis. CONCLUSIONS: CRP is a significant predictor of death in chronic dialysis patients, independent of serum albumin and other possible confounders. Dialysis patients with high CRP levels should be carefully evaluated and monitored regardless of serum albumin concentrations in the normal range.

Blood pressure variability as an adverse prognostic risk factor in end-stage renal disease.

BACKGROUND: Prospective and case-control studies show that blood-pressure variability is an independent risk factor for severe organ damage and cardiovascular events in hypertensives. We prospectively studied the association between systolic blood pressure variability and cardiovascular mortality and mortality from all causes in end-stage renal disease patients. METHODS AND RESULTS: The subjects were 144 patients (86 men, 58 women; mean age+/-SD, 52+/-13 years) who underwent dialysis in the same dialysis centre and were examined for blood-pressure variability. The study period was 38 months beginning in January 1995, during which six cardiovascular and seven noncardiovascular fatalities occurred. Coefficient of variation in systolic blood pressure in 1994, as an indicator of systolic blood pressure variability, ranged from 7.8 to 14.6%. Cumulative incidence of death from all causes was related to coefficient of variation in systolic blood pressure. The difference between the maximum and minimum systolic blood pressure (deltaSBP) in 1994 ranged from 44 to 146 mmHg (mean+/-SD, 78+/-13 mmHg) and correlated significantly with coefficient of variation in systolic blood pressure (r = 0.65, P<0.0001). Cox regression analysis was used to identify the independent predictors for mortality. The hazard ratio for death from all causes increased 1.63 times per 1% increase in coefficient of variation in systolic blood pressure (hazard ratio; 95% confidence interval: 1.63; 1.05-2.53) and 1.03 times per 1 mmHg increase in deltaSBP (1.08; 1.03-1.14). CONCLUSION: These results suggest that systolic blood pressure variability may be a significant prognostic factor in end-stage renal disease.

[A female case of Fournier's gangrene in a patient with lupus nephritis].

Infection is one of the common causes of death in patients with systemic lupus erythematosus (SLE). It is associated with the use of immunosuppressive agents, renal failure, and increased disease activity. Fournier's gangrene is a necrotizing fasciitis occurring in the genital region. It is rare, but can be crucial if surgical drainage is delayed. We report a female case of Fournier's gangrene occurring in a patient with lupus nephritis and chronic renal failure. The patient was a 21-year-old female with chronic renal failure due to lupus nephritis. She had suffered from watery diarrhea one month before admission. It improved after increasing the dose of prednisolone, but, she was complicated with Bartholin abscess. The vaginal pain rapidly spread to the left lower quadrant abdomen despite treatment with oral cephalosporin. Focal incision was performed and black fluid emerged with a foul smell. Pelvic computed tomography (CT) revealed many bubbles in that region. She was found to have septic shock on transfer to our hospital. Thereafter, emergency debridement was performed, followed by antibiotic therapy and hyperbaric oxygen therapy. Organisms were found to be 5 anerobes, such as Bacteroides species, and 3 aerobics, such as Morganella morganii. Fournier's gangrene was improved via these treatments, but she needed maintenance hemodialysis. Fournier's gangrene complication should be considered in SLE with urogenital infection.

The use of a multitracer technique for the studies of the uptake and retention of trace elements in rats.

The uptake by, and distribution and retention of radioactive isotopes in various organs of Wistar rats were examined using the multitracer technique. A hydrocholoric acid solution (pH 3) of a carrier-free radioactive multitracer was prepared from gold foil irradiated with a 14N beam of 135 MeV nucleon. The solution was administered orally to 12 7-week-old male rats. Urine and faeces were collected and each group of three rats was killed at 1, 2, 3 or 6 days after administration. The percentage of administered dose of the 17 elements, Mn, Co, Zn, As, Rb, Sr, Y, Eu, Gd, Er, Tm, Yb, Lu, W, Re, Ir and Pt in the organs blood and excreta were determined using gamma-ray spectrometry. Each element revealed its characteristic distribution among the different organs, including the blood. These results are discussed and compared with those of single-tracer experiments, and the advantages of the multitracer technique are presented.

An epidemiologic analysis of parathyroidectomy in chronic dialysis patients. The Okinawa Dialysis Study Group.

Parathyroidectomy (PTX) is one of the treatments of choice for secondary hyperparathyroidism in chronic dialysis patients. Due to the large increase in long-term dialysis patients, hyperparathyroidism is becoming a common clinical problem. Several studies on PTX have reported various surgical procedures, but limited information is available on the incidence and risk factors of the surgery. The Okinawa Dialysis Study (OKIDS) registry is a community-based dialysis registry. It covers the entire area of Okinawa from when the use of chronic dialysis began in 1971. By the end of 1990, a total of 1,986 chronic dialysis patients were registered and 128 of these had undergone PTX by the end of 1993. The cumulative incidence of PTX was 4.3 in DM and 15.2 in non-DM per 1,000 patient-years. About half of the PTX patients underwent the surgery within 10 years of dialysis. By logistic analysis, the risk of PTX was seen to increase significantly with the duration of dialysis, P < 0.0001. Other clinical variables such as sex, age at the start of dialysis and the presence of diabetes mellitus were not significant predictors of PTX. The probability of PTX increased linearly with the duration of dialysis (r = 0.83, p < 0.0001). After the introduction of active vitamin D in 1981, the probability of PTX was significantly decreased (p < 0.05) compared to the pre-vitamin D period ('71-'80). With prolongation of the duration of dialysis, the risk of PTX increased steadily and was estimated to be 10 percent in 10 years and 20 percent in 20 years. Other uremic factors determining a pathological transformation of parathyroid tissue from reactive to autonomous growth remained to be investigated.

Hypertension in dialysis patients: a cross-sectional analysis.

To clarify the current status of blood pressure control in chronic dialysis patients, we investigated a large group of patients undergoing dialysis in Okinawa, Japan. A set of cross-sectional data of 18 variables, including age, antihypertensive medication, dose of dialysis, blood chemistry findings and predialysis blood pressure, were obtained in 1,243 patients (524 females, 719 males) aged 14 to 93 years who were on hemodialysis in January 1991. Systolic and diastolic blood pressures in patients taking antihypertensive medication (160.8 +/- 0.8/84.6 +/- 0.5 mmHg, mean +/- SEM) were significantly (P < 0.0001) higher than in those were not taking antihypertensive medication (141.3 +/- 0.8/76.9 +/- 0.5). Stepwise regression and univariate analysis methods were used to determine the independent predictors of blood pressure. Antihypertensive medication was positively associated with systolic and diastolic blood pressure. However, the mortality rate of the two groups during the following four years did not differ (antihypertensive-medicated group 23.1% vs. non-medicated group 20.9%). In conclusion, hypertension does not appear to be adequately controlled in our dialysis patients, despite the widespread use of antihypertensive medications.

Multitracer study on uptake and excretion of trace elements in rats.

The multitracer technique was first applied to the investigation of the uptake and excretion behaviour of trace elements in rats. A multitracer solution, prepared by irradiation of a gold target with a 14N-beam from the RIKEN Ring Cyclotron, was orally administered to male Wistar rats. The uptake and excretion rates of 23 elements, Be, Mn, Co, Zn, As, Rb, Sr, Y, Zr, Ce, Pm, Eu, Gd, Tb, Er, Tm, Yb, Lu, Hf, W, Re, Ir and Pt, were simultaneously determined under strictly identical experimental conditions. For some of the elements, the results obtained were consistent with previous reports on uptake and excretion of the elements in animals. For the other elements, unique behaviour was revealed for the first time as described in the present work. These results show that the multitracer technique has excellent reliability and versatility for a comparative study of the uptake and excretion of many different elements in animals.

Alpha 2-adrenoceptors in brain and kidney during development of hypertension in Dahl-Iwai salt-sensitive rats.

BACKGROUND: Both renal and extrarenal factors have been considered to contribute to the development of hypertension in Dahl salt-sensitive rats, but contents of both factors have not been established precisely. AIM: To clarify the role of those factors in the sympathetic nervous system, we examined the regulation of alpha2-adrenoceptors in the lower brainstem and the renal tubular basolateral membranes simultaneously during the development of salt-induced hypertension in Dahl-Iwai salt-sensitive rats. METHODS: Dahl-Iwai salt-sensitive or resistant rats were fed a high (8.0% NaCl)- or low (0.3%)- salt diet from 4 to 6 or 10 weeks of age. At 4, 6 and 10 weeks of age, the plasma membranes of the lower brainstem and the renal tubular basolateral membranes were obtained simultaneously and alpha 2-adrenoceptors were quantified by a radioligand binding assay using 3H-rauwolscine. RESULTS: In the salt-sensitive rats, systolic blood pressure was significantly higher in those fed a high-salt diet than in those fed a low-salt diet. In the salt-resistant rats, both the high- and the low-salt groups showed similar blood pressure levels. At 6 weeks of age, alpha 2-receptor densities of the salt-sensitive rats fed a high-salt diet were lower in the lower brainstem and higher in the renal basolateral membranes than those fed a low-salt diet. In contrast, in the salt-resistant rats, both the high- and the low-salt groups had similar densities. At 10 weeks of age, the difference between the high- and the low-salt groups in the salt-sensitive rats disappeared in both the brainstem and the renal basolateral membranes. CONCLUSIONS: Alpha 2-adrenoceptor regulation in the brainstem and the renal basolateral membranes differs between Dahl-Iwai salt-sensitive and salt-resistant rats. The modulation of alpha 2-adrenoceptors by a high salt intake may be essential particularly in the early phase of the development of salt-induced hypertension.

Alterations of alpha 1-adrenergic receptor densities in right and left ventricles of spontaneously hypertensive rats.

To clarify whether alpha 1-adrenergic receptors contribute to cardiac hypertrophy, we examined alpha 1-adrenergic receptor densities in the right and left ventricles of 5- and 20-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) using [3H]prazosin. Also, we analyzed a pharmacologically distinct subtype of alpha 1-adrenergic receptors by pretreatment with chloroethylclonidine. The ratio of right ventricular weight to body weight as well as left ventricular weight to body weight was higher in SHR than in WKY at 5 weeks of age. At 20 weeks of age, only the left ventricular weight to body weight ratio was higher in SHR. At 5 weeks of age, the right and left ventricular alpha 1-adrenergic receptor densities in SHR were greater than those in WKY (LV 1760 vs. 1275, RV 2543 vs. 1521 fmol/mg protein). At 20 weeks of age, only right ventricular alpha 1-adrenergic receptor density remained higher in SHR (1425 vs. 885 fmol/mg protein). The percentage of pharmacologically distinct alpha 1A receptor was higher in the right ventricle of SHR than in that of WKY at 5 weeks of age (25% vs. 18%). There were no significant differences in the dissociation constants among the alpha 1-adrenergic receptor assays. These findings suggest that an increase in alpha 1-adrenergic receptors might be involved in cardiac hypertrophy in the early phase of hypertension in SHR.

Short-term effects of angiotensin II blockade on renal blood flow and sympathetic activity in awake rats.

To investigate the effects of an angiotensin II type 1 receptor antagonist (CV-11974) on renal blood flow and renal sympathetic nerve activity compared with a calcium antagonist (nicardipine), we measured both parameters in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to 2 days after surgery, CV-11974 (n = 9) and nicardipine (n = 8) were intravenously administered to decrease arterial pressure in a similar time course and degree of hypotension. CV-11974 increased renal blood flow by 23 +/- 4% at the maximal fall in mean arterial pressure (-32 +/- 1 mm Hg), and renal nerve activity increased by 70 +/- 7%. The maximal increase in renal blood flow (+27 +/- 4%) was observed when mean pressure was reduced by approximately 20 mm Hg. The maximal reduction of renal vascular resistance (-33 +/- 3%) correlated significantly with pretreatment levels of plasma renin concentration (r = -.792). In contrast, nicardipine produced a progressive reduction of renal blood flow and marked increases in heart rate and renal nerve activity. Increases in heart rate and nerve activity were greater than those with CV-11974 treatment (P < .001). At the maximal fall in mean pressure (-32 +/- 1 mm Hg), renal blood flow decreased by 23 +/- 4%, which was significantly correlated with percent changes in renal nerve activity (+150 +/- 11%, r = -.744). Renal denervation in another set of rats (n = 6) improved renal blood flow and renal vascular resistance responses to nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs.

To examine the neural effects of antihypertensive drugs on renal blood flow, we measured blood flow and renal sympathetic nerve activity simultaneously in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to two days after surgery, intravenous administration of manidipine (calcium antagonist, n = 10), doxazosin (alpha 1-adrenergic receptor antagonist, n = 9), and clonidine (n = 7) lowered mean arterial pressure by at least 20% from baseline levels. Manidipine initiated a reduction of renal blood flow when mean pressure decreased by 20 +/- 2 mm Hg. At the maximal decrease in renal blood flow (mean pressure, -33 +/- 2 mm Hg), percent decrease in flow (-27 +/- 2%) significantly correlated with percent increase in renal nerve activity (+205 +/- 40%, r = -.878). Doxazosin began to decrease renal blood flow at a level of arterial pressure similar to that in manidipine treatment, whereas the maximal decrease in flow (-19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was significantly less than that in manidipine treatment. Although clonidine decreased arterial pressure and renal nerve activity, renal blood flow did not decrease even at the maximal decrease in mean pressure of 29 +/- 1 mm Hg. The addition of clonidine to manidipine treatment suppressed reflexly enhanced renal nerve activity and restored blood flow to the pretreatment level despite pronounced hypotension. These results clearly demonstrate that antihypertensive drugs with blocking action on renal nerve activity are capable of maintaining renal blood flow and that those associated with reflex-induced enhancement of nerve activity exert deteriorating effects on renal blood flow. Furthermore, a decrease in renal blood flow induced by calcium antagonists is mainly attributed to reflexly enhanced renal nerve activity.