Development and evaluation of a liquid chromatography-mass spectrometry assay and its application for the assessment of renal function.

In the present study we evaluated two commonly used iodinated contrast agents, iohexol and iodixanol, as potential markers of impaired renal function. A reversed phase LC-MS method has been developed in order to separate and quantify the two substances. The assay was linear between 0.02 and 9.7 micromol/L for iohexol and between 0.4 and 49.3 micromol/L for iodixanol (r(2) > 0.998). The recovery during sample preparation ranged from 89.1 to 112.4%. The intra- and inter-assay RSD values were 3.06-13.6% for iohexol and 4.32-12.7% for iodixanol. The validated method was subsequently applied to 17 patients scheduled for angiographic procedure displaying normal and impaired renal function. A mixture of iohexol and iodixanol was intra-arterially injected and their corresponding plasma levels were determined periodically over a 24h period following administration. The elimination of both contrast agents followed by the LC-MS approach allowed us to discriminate between patients with normal and impaired renal function at 4, 8 and 24h after administration. Our preliminary results support the predictive value of iohexol and/or iodixanol clearance in a clinical environment to screen and identify patients at risk of developing CIN.

Evaluation of a new integrated discharge prescription form.

OBJECTIVE: To determine whether a new discharge prescription form which integrates admission medications, in-hospital changes, and discharge medications could enhance the accuracy of information in patient profiles in community pharmacies after hospital discharge. DESIGN: Nonrandomized, prospective, multi-site study. SETTINGS: Internal medicine wards of the three teaching hospitals (1200 beds) of the Centre Hospitalier de l'Université de Montréal. SUBJECTS: Patients admitted to the internal medicine wards between January 4 and 31, 1999, at St.-Luc and Notre-Dame Hospitals formed the control group and received a usual discharge form (UD). Those admitted between February 1 and 28,1999, received the new discharge prescription form (DPF) capturing the list of admission medications and revisions during hospitalization; they served as the experimental group. METHODS: Patient profiles were reviewed to calculate conformity rates of community pharmacy patient profiles after discharge and the rate of overall conformity for each group in the study. Each drug in the patient profile was assessed according to six criteria. Healthcare providers' satisfaction with the DPF was assessed via a written questionnaire. RESULTS: Eighty-nine patients and 669 discharge medications were studied. The patient profiles had a higher conformity rate in the DPF group than in the UD group (82% vs. 40%; p < 0.001); improvement could be attributed to higher conformity rates, particularly for two criteria (medications stopped in hospital and dose changes in hospital). CONCLUSIONS: Integration of admission medications, in-hospital changes, and discharge medications on a single form increases the conformity rates of community pharmacy patient profiles after hospitalization. This tool is well accepted by both pharmacists and physicians and may lead to a major decrease in drug-related problems.

Infrarenal aortic stenosis: value of stent placement after percutaneous transluminal angioplasty failure.

PURPOSE: To evaluate the long-term clinical and hemodynamic effectiveness of aortic stent placement in cases of failure of intended infrarenal percutaneous transluminal aortic angioplasty (PTAA). MATERIALS AND METHODS: Fifty-three patients who underwent technically successful PTAA were compared with 24 patients who underwent aortic stent placement because of PTAA failure (19 patients) or ulcerated lesions (five patients) that otherwise would have been treated surgically because of the embolization hazard associated with PTAA alone. Clinical patency was defined as the absence or improvement of symptoms after the intervention. Hemodynamic patency was defined as a normal Doppler waveform in the common femoral arteries, an ankle-brachial index greater than 0.95, or the absence of a thigh-brachial pressure gradient. RESULTS: Three-year clinical and hemodynamic patency rates, respectively, were 85% and 79% for PTAA and 69% and 43% for aortic stent placement. No morbidity was encountered. With use of the Cox proportional hazards model, two significant risk factors were retained for restenosis: unchanged smoking habit (P =.04) and small dilatation diameter (P =.001). Aortic stent placement, performed in patients with a smaller aortic diameter (10.3 vs. 12.7 mm for PTAA), appeared to be a predictive factor for restenosis by using univariate analysis. By using the Cox proportional hazards model, however, the restenosis rates after PTAA and aortic stent placement were not significantly different. CONCLUSION: When aortic diameter is taken into consideration, there is no evidence that clinical outcome after secondary aortic stent placement would be poorer than technically successful PTAA.

The fainting patient: value of the head-upright tilt-table test in adult patients with orthostatic intolerance.

The head-upright tilt-table (HUT) test is used primarily for the investigation of orthostatic symptoms. Although this test is frequently the gold standard for the evaluation of neurocardiogenic syncope, dysautonomia and postural orthostatic tachycardia syndrome, there is a debate over its diagnostic value and method. The authors review the physiologic basis of the HUT test, the method, patterns of response, indications and contraindications, and diagnostic validity. Despite its limitations, the HUT test is useful in patients with a variety of clinical manifestations induced by orthostatism. It is most useful in documenting objective measures of orthostatic hypertension that cannot be obtained in a clinical setting.

[Calcium channel blocking agents and albuminuria in diabetic and hypertensive patients. A pilot study]. / Agents bloqueurs des canaux calciques et albuminurie des sujets diabétiques et hypertendus. Une étude pilote.

UNLABELLED: Diltiazem tends to decrease proteinuria in hypertensive diabetic subjects in comparison to amlodipine that does not modify it. Since estimated glomerular pressure is identical in amlodipine treated and diltiazem treated subjects, differences in albuminuria may be explained by different renal tubular reabsorption rates. OBJECTIVES: To compare plasma clearances (PC) of technetium labeled albumin (albumin-Tc99m) obtained by serial plasma measurements with PC obtained by urinary excretion measurements. Indirectly evaluate tubular reabsorption of albumin-Tc99m. Test the hypothesis that amlodipine decreases renal tubular reabsorption of albumin in diabetic hypertensive subjects. METHODS: Fourteen diabetic and hypertensive subjects (DH) (average plasma creatinine: 94 mmol/L) and 6 normal subjects (average plasma creatinine: 82 mmol/L) had previously been assessed for albumin-Tc99m PC. Eleven of these 14 DH subjects were then randomized to diltiazem 300 mg/daily (6 subjects) or amlodipine 10 mg/daily (5 subjects). Their glomerular filtration, glomerular pressure and albumin-Tc99m PC were then assessed on the 3rd, 6th, and 12th month of the study. RESULTS: Albumin-Tc99m PC obtained from serial blood draws: A decrease in PC between months 0 and 3 from 14 to 10.6 cc/min was observed in subjects treated with amlodipine but subjects on diltiazem showed PC stability (from 11.9 to 12 cm3/min). PC obtained from urinary excretion: Amlodipine and diltiazem treated subjects showed PC stability. Plasma volume in amlodipine treated subjects decreased from 156 to 127% and diltiazem treated subjects from 128 to 117%. CONCLUSION: A decrease in PC obtained with plasma measurements and stability of PC based on urinary excretion measurements tends to identify a decrease in plasma volume. A decrease in albumin-Tc99m tubular reabsorption was not observed. The estimate of albumin PC with Tc 99m labelled albumin measurements still needs to be validated.

Recurrent use of newer oral contraceptives and the risk of venous thromboembolism.

The epidemiological studies that assessed the risk of venous thromboembolism (VTE) associated with newer oral contraceptives (OC) did not distinguish between patterns of OC use, namely first-time users, repeaters and switchers. Data from a Transnational case-control study were used to assess the risk of VTE for the latter patterns of use, while accounting for duration of use. Over the period 1993-1996, 551 cases of VTE were identified in Germany and the UK along with 2066 controls. Totals of 128 cases and 650 controls were analysed for repeat use and 135 cases and 622 controls for switching patterns. The adjusted rate ratio of VTE for repeat users of third generation OC was 0.6 (95% CI:0.3-1.2) relative to repeat users of second generation pills, whereas it was 1.3 (95% CI:0.7-2.4) for switchers from second to third generation pills relative to switchers from third to second generation pills. We conclude that second and third generation agents are associated with equivalent risks of VTE when the same agent is used repeatedly after interruption periods or when users are switched between the two generations of pills. These analyses suggest that the higher risk observed for the newer OC in other studies may be the result of inadequate comparisons of pill users with different patterns of pill use.

Octreotide for orthostatic hypotension.

A patient suffering from multiple system atrophy (Shy-Drager syndrome) with severe symptomatic postprandial orthostatic hypotension was treated. Because the disease was progressively refractory to fludrocortisone and midodrine, octreotide was introduced subcutaneously (25 micrograms before meals). Beneficial effects were clearly noted by the patient and documented by repeated tilt table testing with and without the octreotide. The literature on the physiological actions of octreotide and the clinical evidence supporting its use are reviewed briefly. Octreotide mainly mediates splanchnic venoconstriction, which explains its beneficial effects. It is a useful adjunct for the short term treatment of orthostatic hypotension associated with dysautonomia. Its long term efficacy and safety need to be studied.

Infrarenal aortic stenosis: long-term clinical and hemodynamic results of percutaneous transluminal angioplasty.

PURPOSE: To evaluate the safety and long-term clinical and hemodynamic results of percutaneous transluminal angioplasty (PTA) of the infrarenal aorta. MATERIALS AND METHODS: During nearly 10 years, 102 patients with symptomatic infrarenal atherosclerotic aortic stenosis underwent PTA. Follow-up information was available in 92 patients (17 men, 75 women; mean age, 51.9 years). Stenosis involved the aortic bifurcation in 18 patients and only the infrarenal abdominal aorta in 74 patients. Technical success was defined as residual stenosis less than 50% or a pressure gradient less than 10 mm Hg after PTA. Clinical patency was defined as the absence or improvement of symptoms after PTA. Hemodynamic patency was defined as a normal Doppler waveform in the common femoral arteries, an ankle-brachial ratio greater than 0.95, or the absence of a thigh-brachial pressure gradient. RESULTS: Technical success was achieved in 78 patients after PTA. After 10 years, primary clinical and hemodynamic patency rates were 72% and 46%, respectively. After a mean follow-up of 51 months, 15 of the 22 symptomatic recurrences were due to aortic restenosis; 11 of these were treated with repeated PTA with or without stent placement, and three eventually required aortic surgery. No morbidity was encountered. CONCLUSION: Infrarenal aortic PTA proved to be safe and provided durable, long-term clinical improvement. In this group of relatively young patients, the clinical patency rate of PTA was equivalent to that of aortic surgery but with less morbidity.

Altered regulation of natriuretic peptides in the rat heart by prenatal exposure to morphine.

1. Both endogenous and exogenous opioids modulate blood pressure and cardiac function by stimulating cardiac synthesis of atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP). Since morphine crosses the placental barrier, it could alter the ANF-BNP system in the fetal heart. The aim of this study was to characterize cardiac natriuretic peptides in normal rat development and in rats prenatally exposed to morphine. 2. Female rats received either saline or morphine (10 or 20 mg kg-1 day-1) via osmotic minipumps during gestation. The effects of this treatment were investigated in offspring at 1, 4 and 22 days of age. 3. During maturation, atrial ANF and ANF mRNA increased by 3-fold from birth to 3 weeks of age, but BNP and BNP mRNA tended to decrease. In the ventricles, both ANF and BNP content decreased at 3 weeks after birth, from 25.11 +/- 3.6 to 0.81 +/- 0.1 ng (mg protein)-1 (P < 0.001), and from 3.36 +/- 0.33 to 0.19 +/- 0.01 ng (mg protein)-1 (P < 0.001), respectively. However, whereas ventricular ANF mRNA decreased, BNP mRNA levels did not change during maturation. Prenatal exposure to morphine significantly increased ANF content in the left atria of 22-day-old rats, and in the right atria of 1-, 4- and 22-day-old rats compared with age-matched saline controls. In contrast, prenatal exposure to 20 mg kg-1 day-1 morphine significantly inhibited BNP and BNP mRNA in the ventricles at all ages studied. 4. These observations suggest that alterations in mRNA synthesis or stability and/or post-translational processing of ANF and BNP occur in the heart during maturation, and that prenatal exposure to morphine alters cardiac production, and possibly release, of both peptides.

Percutaneous biliary drainage: clinical trial of analgesia with interpleural block.

PURPOSE: To determine the analgesic efficacy and safety of interpleural block for percutaneous biliary drainage. MATERIALS AND METHODS: In this double-blind study, 34 age- and sex-matched patients who were to undergo percutaneous biliary drainage because of malignant biliary obstruction were randomly assigned to the true-block group (30 mL 0.5% bupivacaine block) or placebo-block group; all had access to a patient-controlled analgesia (fentanyl) pump. Self medication, pain reports, blood pressure, heart rate, and oxygen saturation were monitored during and until 8 hours after drainage. The McGill Pain Questionnaire was administered 1 hour after biliary drainage. RESULTS: Patients in the placebo group self administered statistically significantly more fentanyl than did patients in the true-block group (P = .008). Peak pain scores (10-point scale) and McGill Pain Questionnaire scores were statistically significantly higher for the placebo group patients (P = .017 and P = .001, respectively). There were no differences between groups in terms of blood pressure, heart rate, and oxygen saturation. Two patients had pneumothorax caused by the interpleural block. CONCLUSION: Interpleural block was effective in decreasing pain and opioid requirements during and after percutaneous biliary drainage and did not compromise the cardiopulmonary status of the patient. However, the rate of pneumothorax was higher than previously reported.

First-time use of newer oral contraceptives and the risk of venous thromboembolism.

Recent epidemiologic studies reported that the risk of venous thromboembolism (VTE) was higher with the use of the newer third generation oral contraceptives than with second generation agents. Although the overall findings of these studies are similar, the results, as they relate to patterns and duration of oral contraceptive use particularly among first-time users, are inconsistent. We reanalyzed data from the Transnational case-control study to assess the risk of VTE associated with first-time use of oral contraceptives as a function of its duration of use. Over the period 1993 to 1995, 471 cases of venous thromboembolism were identified in Germany and the United Kingdom. For each case, up to four controls were obtained, for a total of 1772 controls. Data on oral contraceptive use and confounding variables, including data on sociodemographic, lifestyle, medical history, and family history of disease, were obtained by interview. Data analysis was based on the 105 cases and 422 controls who were first-time users of second or third generation agents, or never users of oral contraception. Rate ratios, adjusted for confounders and approximated by odds ratios, were estimated as a continuous function of duration of oral contraceptive use by logistic regression and quadratic spline models. We found, for first-time users, that the adjusted rate ratio of VTE as a function of the duration of oral contraceptive use is essentially identical for second and third generation pills relative to never users. This rate ratio increases to around 10 in the first year of use and decreases to around two after 2 years of use, remaining at this risk level thereafter for both second and third generation agents. We conclude that second and third generation agents are associated with identical risks of venous thromboembolism when they are prescribed to women who are using oral contraceptives for the first time ever.

PIP: Recent epidemiologic studies reported that the risk of venous thromboembolism (VTE) was higher with the use of the newer third-generation oral contraceptives (OCs) than with second-generation agents. Although the overall findings of these studies are similar, the results, as they relate to patterns and duration of OC use, particularly among first-time users, are inconsistent. The authors reanalyzed data from the transnational case-control study to assess the risk of VTE associated with first-time use of OCs as a function of its duration of use. Over the period 1993-95, 471 cases of VTE were identified in Germany and the UK. For each case, up to 4 controls were obtained, for a total of 1772 controls. Data on OC use and confounding variables, including data on sociodemographic, lifestyle, medical history, and family history of disease, were obtained by interview. Data analysis was based on the 105 cases and 422 controls who were first-time users of second- or third-generation agents or never-users of OCs. Rate ratios, adjusted for confounders and approximated by odds ratios, were estimated as a continuous function of duration of OC use by logistic regression and quadratic spline models. The authors found, for first-time users, that the adjusted rate ratio of VTE as a function of the duration of OC use is essentially identical for second- and third-generation pills relative to never-users. This rate ratio increases to about 10 in the first year of use and decreases to about 2 after 2 years of use, remaining at this risk level thereafter for both second- and third-generation agents. The authors conclude that second- and third-generation agents are associated with identical risks of VTE when they are prescribed to women who are using OCs for the first time ever.

Abnormal adrenal and vascular responses to vasopressin mediated by a V1-vasopressin receptor in a patient with adrenocorticotropin-independent macronodular adrenal hyperplasia, Cushing's syndrome, and orthostatic hypotension.

The elucidation of gastric inhibitory polypeptide-dependent Cushing's syndrome suggested that ectopic expression or increased responsiveness of other adrenal hormone receptors may underlie ACTH-independent macronodular adrenal hyperplasia (AIMAH) or adrenocortical tumors. We studied a 36-yr-old woman with Cushing's syndrome, AIMAH, and orthostatic hypotension. During upright posture, cortisol and aldosterone were stimulated despite suppression of ACTH and renin. Arginine vasopressin (AVP, 10 U im), under dexamethasone suppression, increased plasma cortisol (3.4-fold), aldosterone (67-fold), and androgens in this patient but not in controls. ACTH 1-24, but not desmopressin acetate, angiotensin II, isoproterenol, or other hormones stimulated steroidogenesis in vivo. Plasma AVP was undetectable initially and increased suboptimally during posture tests after bilateral adrenalectomy. AVP stimulated cortisol production more in dispersed cells from the AIMAH than from a normal adult adrenal (424 vs. 135% at 10 nmol/L). Adrenal V1-AVP receptor presence and mediation of response were shown by RT-PCR and by binding and [Ca+2]i studies. Post adrenalectomy, orthostatic hypotension persisted; a prolonged vasoconstrictive response to AVP was found in vitro in the patient's sc small arteries. We propose that altered adrenal and vascular responses of the V1-AVP receptor-effector pathway underlie this new syndrome.

Single-dose pharmacokinetics of ampicillin and tobramycin administered by hypodermoclysis in young and older healthy volunteers.

1. To test the feasibility of administering antibiotics by subcutaneous infusion to the elderly, we compared the pharmacokinetics of tobramycin (single dose of 80 mg) given by hypodermoclysis (HDC) with the kinetics of the antibiotic injected intravenously (i.v.) in 10 young (< 50 years old) and 10 elderly (> 65 years old) healthy volunteers. Similar studies were performed with ampicillin (single dose of 1 g) in 12 young and 10 older healthy volunteers. 2. Compared with the i.v. route, HDC delayed the time to reach the maximal plasma concentration (tmax) of tobramycin in young volunteers: 32 +/- 6 (s.d.) min vs 88 +/- 46, P < 0.005, and older volunteers: 27 +/- 4 min vs 89 +/- 15, P < 0.005. Administration of the antibiotics by HDC was well tolerated. The plasma concentration of tobramycin 30 min after the end of infusion (C60) was lower (P < 0.05) following HDC than after the i.v. route in both young, 2.2 +/- 0.7 vs 3.5 +/- 0.8 micrograms ml-1, and elderly subjects, 2.2 +/- 0.8 vs 3.8 +/- 0.9. micrograms ml-1. 3. The area under the curve (AUC) of tobramycin given by HDC was slightly smaller than when given i.v., i.e. in young subjects: 740 +/- 225 (s.d.) vs 893 +/- 223 micrograms ml-1 min, NS, and in the elderly: 980 +/- 228 vs 1056 +/- 315 micrograms ml-1 min, NS. 4. When ampicillin was administered by HDC, the tmax was also delayed in young volunteers: 45 +/- 18 vs 23 +/- 6 min, and in the elderly: 49 +/- 18 vs 27 +/- 4 min, P < 0.005, the AUC was greater by HDC than i.v. in the young volunteers: 4527 +/- 1658 micrograms ml-1 min vs 3810 +/- 1033 micrograms ml-1 min and in the elderly: 6795 +/- 2094 micrograms ml-1 min vs 4217 +/- 1518 micrograms ml-1 min, and the C60 was higher by HDC in the young: 27 +/- 7 vs 24 +/- 9 micrograms ml-1, and in the elderly: 32 +/- 9 vs 23 +/- 11 micrograms ml-1, P < 0.05. 5. In conclusion, HDC delays the entry of the antibiotic into the systemic circulation, but did not affect the amount available. HDC was well tolerated and could become an adequate method for antibiotic administration to the elderly.

Comparison of streptokinase and urokinase in local thrombolysis of peripheral arterial occlusions for lower limb salvage.

PURPOSE: To compare the efficacy and safety of streptokinase (SK) and urokinase (UK) in the treatment of local thrombolysis. PATIENTS AND METHODS: Over a 24-month period, 40 patients with 45 lower limb arterial occlusions of less than 45 days duration underwent intraarterial fibrinolysis. Twenty occlusions were treated with recombinant UK and tissue culture-derived UK, and 25 occlusions were treated with SK. The study was retrospective, but the two groups were very homogeneous in terms of vascular surgical history, medical risk factors, and occlusion characteristics. RESULTS: Complete lysis (95% or more) was achieved in 84% of SK infusions and 89% of UK infusions. Endoluminal and surgical interventions as well as clinical outcomes of SK and UK treatment were comparable. However, infusion time was significantly longer for SK treatment: 28.5 hours versus 19.1 hours for UK treatment (P = .035). Complication rates were not statistically significantly different. Average length of stay in the intensive care unit was identical (2.2 days) for both groups, and the difference in hospital stay was not statistically significant (7.7 days for SK vs 8.7 days for UK). CONCLUSION: At the concentrations and doses used, the efficacy and safety of SK and UK were comparable, despite longer SK infusion time.

Prostaglandins and renal function in hypertensive patients with unilateral renal artery stenosis and patients with essential hypertension.

OBJECTIVE: This study was designed to compare the effects of prostaglandin synthesis inhibition on calculated preglomerular and postglomerular resistance in hypertensive patients with unilateral renal artery stenosis (RAS) and in patients with essential hypertension. DESIGN AND METHODS: Sixteen patients with suspected renovascular hypertension underwent renal angiography: eight had unilateral renal artery stenosis > or = 70% and eight had normal angiograms or stenosis < or = 40%. Radionuclide renography and 6 h urinary collection were performed twice for each subject, at baseline and after indomethacin administration. Levels of urinary vasodilatory prostaglandins were measured by specific radioimmunoassays. Visual image analysis was performed to determine the parenchymal transit time (PTT). The glomerular filtration rate (GFR) was calculated from the plasma clearance of [99mTc]-diethylenetriamine pentaacetic acid (DTPA). The preglomerular and postglomerular resistances were estimated according to Gomez's equations. RESULTS: The prostaglandin excretion decreased significantly after indomethacin administration both in RAS and in essential hypertension patients. The PTT increased from 230 +/- 10 to 340 +/- 40s in the stenotic kidney compared with the contralateral kidney and the kidneys of essential hypertension patients. The GFR was decreased both in stenotic and in contralateral kidneys (48 +/- 4 to 37 +/- 5 and 60 +/- 4 to 52 +/- 5 ml/min, respectively) but did not decline in the kidneys of essential hypertension patients. The preglomerular resistance increased both in stenotic and in contralateral kidneys, whereas it did not rise significantly in the kidneys of essential hypertension patients. The postglomerular resistance in stenotic and contralateral kidneys of RAS patients was not altered. CONCLUSIONS: Prostaglandins limit GFR decreases in RAS by preventing preglomerular constriction without interfering with postglomerular constriction. Thus, the action of vasoactive prostaglandins on preglomerular resistance might maintain renal function in the short term by limiting the fall in GFR in the stenotic kidney and by increasing the GFR in the contralateral kidney.

The Drug Utilization Review Network of Quebec.

Drug utilization review programs have been recognized as an effective way to control health care spending while maintaining quality services. This article describes the structure, mandate and activities of Quebec's Drug Utilization Review Network. This 112-member network, which represents 45% of health care facilities in the province, was established to promote the optimal utilization of drugs through the provision of support to pharmacology committees, therapeutic committees and pharmacy departments. The network's main role is to coordinate multi-centre drug utilization studies. Future challenges include maintaining member interest and evaluating the clinical and economic impact of the network's efforts.

Negative chronotropic effect of the atrial natriuretic peptide in an anesthetized dog model.

The effects of atrial natriuretic peptide (ANP) on heart rate and on the chronotropic response induced by angiotensin II were evaluated. The action of angiotensin II, injected into the sinus node artery, on heart rate was determined in anaesthetized and vagotomized dogs pretreated with beta-adrenoceptor antagonist (n = 9), before and after the infusion of physiological and pharmacological doses (10 and 50 ng/kg per min) of ANP. ANP plasma concentrations were determined by radioimmunoassay. Compared to the baseline concentration values (117 +/- 3 pg/ml), a slight increase was produced by the lower dose (293 +/- 45 pg/ml), whereas a significant augmentation was noted with the higher dose of ANP (1024 +/- 255 pg/ml). The basal heart rate and mean systemic arterial pressure were decreased (26.3 and 13.5%) during the intravenous infusion of the physiological dose of the peptide and were significantly reduced (32.5 and 29.2%, P < 0.05) by the administration of the pharmacological dose of ANP. Angiotensin II had a positive chronotropic effect (29 +/- 3 beats/min) that was significantly inhibited by the pharmacological dose of ANP. Our results suggest that ANP might have a role in the control of heart rate.

Renal effects of immersion in essential hypertension. Carvedilol Study Group.

Plasma concentrations of atrial natriuretic factor (ANF) have been reported to be unchanged or increased in patients with essential hypertension. Head out of water immersion (HOI) in a thermoneutral bath induces diuresis and natriuresis, an increase in plasma ANF, and reductions in plasma renin activity and aldosterone concentrations. HOI was used in this study to stimulate the secretion of ANF, and compare its release in patients with essential hypertension (EH) (n = 14) and normotensive subjects (n = 13). Renal function changes induced by HOI were also monitored. HOI that lasted 2 h was compared with a control-seated period in each subject. Blood pressure was significantly reduced (P < .05) in normotensive controls from 112 +/- 3/74 +/- 2 to 100 +/- 3/61 +/- 2 mm Hg, and in patients with EH from 137 +/- 4/93 +/- 3 to 123 +/- 3/78 +/- 2 mm Hg. Plasma levels of ANF increased significantly (P < .05) in both groups from 5.9 +/- 1.3 to 16.3 +/- 3 pmol/L in normotensive controls and from 6.0 +/- 0.9 to 13.2 +/- 2.5 pmol/L in patients with EH. Plasma cyclic guanosine monophosphate concentrations increased more (P < .05) in the patients with EH (3.9 +/- 0.4 to 6.1 +/- 0.5 nmol/L) than in controls (3.4 +/- 0.3 to 4.8 +/- 0.4 nmol/L), whereas plasma renin activity levels decreased in controls (2.29 +/- 0.58 to 1.63 +/- 0.55 ng/mL/h) and to a greater degree in patients with EH (1.62 +/- 0.52 to 0.77 +/- 0.19 ng/mL/h, P < .05) by HOI.(ABSTRACT TRUNCATED AT 250 WORDS)