The effect of spironolactone on lipid, glucose and uric acid levels in blood during long-term administration to hypertensives.

Spironolactone, an aldosterone antagonist, was given in a daily dose of 100 mg to 15 patients with primary hypertension for one year. Fasting levels of lipids, uric acid, glucose, insulin, potassium and growth hormone were measured before and after 6 and 12 months of treatment. Total cholesterol, LDL cholesterol, glucose, potassium and growth hormone were unchanged, HDL cholesterol fell from (mean +/- SD) 1.5 +/- 0.6 to 1.1 +/- 0.3 mmol/l (p less than 0.05) after 6 months of treatment and remained lowered (1.0 +/- 0.3 mmol/l) (p less than 0.01) after 12 months of treatment. There was a transient fall after 6 months of treatment in triglycerides from 2.4 +/- 1.5 to 2.0 +/- 1.1 mmol/l (p less than 0.05), uric acid from 380 +/- 73 to 342 +/- 58 mumol/l (p less than 0.05) and an increase in insulin from 16 +/- 9.5 to 28.6 +/- 26.8 mU/l (p less than 0.05). The blood glucose curves above fasting levels after glucose loading were unchanged during spironolactone treatment, whereas the area under the net insulin curve was higher after 6 months of treatment (163 +/- 103 mU X h/l) than before treatment (105 +/- 71 mU X h/l), indicating a small and transient insulin resistance. Thus, spironolactone impaired the glucose tolerance transiently and gave small and almost transient changes in fasting serum lipid and uric acid levels.

Clinical chemical analyses of serum obtained from capillary versus venous blood, using Microtainers and Vacutainers.

The concentrations of sixteen chemical constituents determined in specimens from skin puncture serum (capillary serum) collected in Microtainer were compared to the concentrations in venous serum collected in Vacutainer from adult individuals. Compared to venous serum, the concentrations in skin puncture serum were higher for potassium (2.9%), chloride (2.3%) and thyroid stimulating hormone (TSH) (86.7%) and lower for sodium (1.6%), calcium (3.2%), phosphorus (5.0%), creatinine (6.6%) and total protein (4.7%), whereas no differences were observed for urea, bilirubin, ASAT, ALAT, LD, insulin and thyroxin. The differences for sodium, calcium and TSH are explained by interference form the sampling device (Microtainer). Except for TSH, the differences are small and probably of minor clinical importance.

The influence of dihydralazine and angiotensin-II blockade on renal extraction of [131I]hippuran.

The renal extraction of [131I]ortho-iodohippuran ([131I]OIH) was measured during the first minutes after the bolus injection during renal vein catheterization of two groups of hypertensive patients. Concomitantly the hippuran clearance (effective renal plasma flow (ERPF) was determined with a quantitative renographic technique based on net kidney uptake between 1 1/2 and 2 1/2 min and plasma radioactivity 2 min after the bolus injection of hippuran. The study was repeated 30 min after intravenous administration of dihydralazine (0.1 mg/kg body weight) in 14 subjects (group A) and during continuous infusion of the angiotensin II blocking agent Saralasin (5 micrograms/kg . min) in 10 subjects (group B). Before dihydralazine was given, the rate of [131I]OIH extraction was (Mean +/- S.D.) 74.0 +/- 16.7% in the 2 min sample after bolus injection of hippuran, 67.5 +/- 17.3% after 10 min, falling to 53.0 +/- 15.3% after 30 min. There was no difference after dihydralazine administration, as the extraction values were 75.6 +/- 17.5 and 65.6 +/- 21.4% 2 and 10 min after the bolus injection of hippuran. The extraction values before Saralasin infusion were 74.2 +/- 15.7%, 59.8 +/- 18.2% and 47.1 +/- 16.6% at 2, 10 and 25 min after bolus injection of hippuran. Saralasin elicited no change in the extraction, as the values were 74.1 +/- 18.6% and 64.3 +/- 23.2%, 2 and 10 min after hippuran injection. For kidneys with ERPF above 100 ml/min . 1.73 m2 the extraction 2 min after hippuran injection was at the level of 82%, whereas the extraction fell rapidly with further reduction in ERPF. It is concluded that ERPF determined with the renographic technique, reflects the renal plasma flow when the clearance for the individual kidney exceeds 100 ml/min . 1.73 m2. This is the case also after dihydralazine and Saralasin administration.

Haemodynamic effects of treatment and withdrawal of spironolactone in essential hypertension.

The effect of spironolactone (50 mg b.i.d.) in essential hypertension was studied by measurement of effective renal plasma flow (ERPF), blood urea nitrogen (Ur+), serum creatinine (Cr), cardiac index (CI), plasma volume (PV), body weight (BW), mean arterial blood pressure (MAP), total peripheral resistance index (TPRI), plasma renin activity (PRA) and plasma aldosterone (PA) in two groups of patients. Ten cases had determinations before, after 5 weeks and 4 months of treatment; fourteen cases who had been treated at an average of 18 months, had measurements while on treatment and 5 weeks after cessation of the drug. Among the ten patients ERPF fell in six and increased in four patients during treatment, but was statistically unchanged in the total group. Ur + and Cr were also unchanged by treatment. ERPF was unchanged after withdrawal of the drug. During treatment BW decreased 3.5%, PV decreased in nine and increased in one patient, while PRA and PA increased 426% and 202%, respectively. After cessation of the aldosterone blockade, BW increased 1.9%, PV 10.5% while PRA and PA fell 60% and 48.9%, respectively. MAP fell in eight out of ten patients during treatment. This fall was associated with a fall in CI or TPRI, or both. After withdrawal of the drug, MAP increased in nine and decreased in five of the patients. The data shows that this dosage of spironolactone gave minor adjustments of the systemic and renal circulation in spite of the consistent changes in BW, PV, PRA and PA.

Pulmonary blood volume and interventricular circulation time in physically trained and untrained subjects.

Resting pulmonary plasma and blood volumes (PPV and PBV), interventricular circulation time (IVCT), cardiac and stroke index (CI and SI), heart rate (HR), total plasma and blood volumes (PV and BV) were determined in athletes (two male groups representing different types of sport activities, and one female group) and compared with those of non-athletes (one male and one female group). In addition to high maximal aerobic power, the athletes were characterized by greater SI, BV and PV and lower resting HR than non-athletes, PPV and PBV were significantly larger and IVCT significantly longer in the trained than in the untrained groups, probably reflecting an improved capacity of the pulmonary circulation. PPV as per cent of PV was almost equal in all the groups, indicating the same distribution of plasma between the pulmonary and systemic circulation. The data also indicate that total blood volume is an important determinant of the magnitude of the pulmonary vascular bed. The increased volume of flowing blood and increased stroke volume in athletes probably allows for a reduction in flow velocity and thereby a reduction in kinetic energy.

Decreased renal plasma flow during propranolol treatment in essential hypertension.

The pharmacodynamic effect of propranolol (80 mg b.i.d.) on the renal and systemic circulation was studied after 1 and 8 months of treatment in 13 patients with essential hypertension, using non-invasive radioisotope techniques. Effective renal plasma flow (ERPF) fell from (mean +/- S.E.M.) 244 +/- 18 to 208 +/- 14 after 1 month and to 187 +/- 13 ml/min.m2 after 8 months of treatment. Concomitantly cardiac index (CI) fell from 3.24 +/- 0.15 to 2.62 +/- 0.11 and 2.75 +/- 0.10 l/min.m2, respectively. The coefficient of correlation between the decreases in ERPF and CI was 0.49. Mean arterial blood pressure decreased from 138 +/- 5 to 118 +/- 5 and 116 +/- 4 mmHg, respectively. Left ventricular work was reduced by 30.2 and 27%, while peripheral resistance was unchanged. Total plasma volume was increased from 19.3 +/- 0.5 to 20.3 +/- 0.6 ml/cm after 1 month, but was within the same range as the control values after 8 months of treatment. Pulmonary plasma volume was unchanged, indicating that there was no pooling of plasma in the pulmonary circulation. The interventricular circulation time was increased from 6.9 +/- 0.4 s to 8.4 +/- 0.3 s and varied with the change in heart rate. It is concluded that the fall in ERPF might be explained by reduced cardiac output in addition to interference with the hemodynamic autoregulation in the kidney.

113mIn-DTPA, a useful compound for the determination of glomerular filtration rate (GFR). The binding of 113mIn to DTPA and a comparison between GFR estimated with 113mIn-DTPA and 125I-iothalamate.

For measurement of glomerular filtration rate the usefulness of diethyl traimino penta acic (DTPA) labelled with 113mIndium has been explored. The labelling procedure is very simple, since eluate from an 113mIn generator can be used directly for labelling DTP. The in vitro and in vivo binding of 113mIn to DTPA in competition with serum proteins was studied by gel-filtration. The radioactivity with the 113mIn-DTPA peak represented 100.6, 107.1 and 99.6% of the amount of radioactivity applied to the gel column for the in vivo studies, and 102.0 and 101.4% for the in vitro studies. Futhermore, the clearance of 113mIn-DTPA was compared to the clearance of 125I-iothalamate using the constant infusion technique. The clearance values were found to be nearly equal (r=0.996). It is concluded that 113mIn is almost entirely bound to DTPA after intravenous injection of the 113mIn-DTPA complex, and that the complex is a suitable agent for determination of glomerular filtration rate.

Renal plasma flow and cardiac output during hydralazine and propranolol treatment in essential hypertension.

Eleven patients with essential hypertension were given hydralazine (25 mg b.i.d.) for 2 weeks, hydralazine and propranolol (80 mg b.i.d.) for the next 2 weeks, and propranolol alone for the last 2 weeks. The changes in the renal and systemic circulation elicited by the drugs were studied before start of medication and bi-weekly during the treatment, using non-invasive radioisotope techniques. Hydralazine alone did not alter mean arterial blood pressure (MAP), heart rate (HR), cardiac index (CI), effective renal plasma flow (ERPF), peripheral renin activity (PRA) and plasma aldosterone (Aldo) but when propranolol was added MAP fell 15.2%, HR 22.5% and CI 18.4%, while ERPF was unchanged. When hydralazine was withdrawn and propranolol was given alone, ERPF decreased 13.2%. Plasma aldosterone was unchanged, whereas PRA decreased during propranolol treatment. The reduction in ERPF elicited by propranolol, was highly significant (P less than 0.01). From the test sequence it appears that dihydralazine prevents this effect of propranolol on kidney function. These findings might have a direct bearing on the choice of antihypertensive treatment.

The cardiac response to a small i.v. dose of dihydralazine, a safe drug for diagnostic tests?

Dihydralazine, given in small i.v. doses, has been of great value in diagnostic tests for unilateral renovascular hypertension, where it enhances renin release on the affected side. The acute hemodynamic effects of an i.v. dose of 0.1 mg/kg b.wt. were studied in 14 patients with essential hypertension, using a quantitative renographic technique for determination of effective renal plasma flow and radiocardiographic technique for determination of the parameters in systemic circulation. Cardiac index increased from 4.040 to 6.423 1/min.m2 (p less than 0.01), stroke index from 59 to 66 ml/beat.m2 (p less than 0.05), heart rate from 70.4 to 96.6 beats/min (p less than 0.01) and left ventricular work index from 1.04 to 1.49 W/m2 (p less than 0.01), while mean arterial B decreased from 125 to 110 mmHg (p less than 0.01) and total peripheral resistance index from 2927 to 1534 10(5).N.s.m(-3) (p less than 0.01). Effective renal plasma flow and pulmonary plasma volume were unchanged. Peripheral renin activity increased from 0.5 to 1.6 nmol A1/1.h (p less than 0.02). It is concluded that even a small test dose of 0.1 mg/kg of dihydralazine elicits a considerable additional work load on the heart, a circumstance that must be taken into consideration in studies of patients with coronary heart diseases.