The effects of synthetic human atrial natriuretic peptide (hANP) on arterial blood pressure, heart rate, and renal functions were evaluated in conscious trained dogs in moderate sustained water diuresis. Synthetic hANP was given i. v. over 3 min at doses of 0.27–2.16 μg kg ‐1 body wt. It did not cause significant changes in blood pressure or heart rate. The rate of sodium excretion increased 20‐fold following 2.16 μg kg ‐1 and 2.5‐fold after 0.54 μg kg ‐1 . Natriuresis was immediate and vanished after 10 min, regardless of dose. The concomitant increase in diuresis was less than 50%, but significant for a longer period of time. Increases in potassium excretion were significant, but small, that is, by a factor of 1.5–2.8. All natriuretic doses of hANP increased PAH clearance (at constant blood pressure), but some did so without measurably affecting creatinine clearance.
The recently discovered mycoplasma species Mycoplasma genitalium was isolated from urethral specimens from men with nongonococcal urethritis (Tully et al., Lancet i:1288-1291, 1981). In a previous report (K. Lind, Lancet ii:1158-1159, 1982), prominent serological cross-reactions were demonstrated between this mycoplasma and M. pneumoniae. In the present study, the two mycoplasma species were compared more extensively. In classical mycoplasma medium without thallium acetate, M. genitalium grew more slowly than M. pneumoniae did but finally formed similar amounts of acetic acid and lactic acid from glucose. Although their colonies on solid medium were indistinguishable, transmission electron microscopy showed that the flask-formed cells of M. genitalium (especially their necks) were shorter than those of M. pneumoniae. The two species were distinct since DNA hybridization showed only 1.8% homology in base sequences, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed significantly different profiles of the two strains. However, considerable similarities were found in their antigenic reactions in various serological tests. The presence of common or closely related antigens was demonstrated in the two species with rabbit immune sera in complement fixation test with chloroform-methanol-extracted antigens by an indirect immunofluorescence test on microcolonies, and by metabolism inhibition and growth inhibition tests. Cross-reactions were also demonstrated by crossed immunoelectrophoresis. The role of M. genitalium as a human pathogen in the genital tract has not been assessed. If serological tests are to be used in this assessment, caution must be exercised due to the extensive cross-reactions demonstrated. Some of the species-specific antigens which we have demonstrated would be appropriate for use in such tests and would help to circumvent problems caused by cross-reactions.
Summary. Arterial plasma immunoreactivity of endogenous human α‐atrial natriuretic peptidei 1–28 (ANP) underwent mean 54%, 28% and 40% extraction during one passage through the circulation in the kidney ( n = 12), liver‐intestine ( n =14) and lower limb ( n = 8), respectively, in supine fasting subjects with no detectable disease or subjects with cardiovascular or hepatic disorders of minor degree undergoing a haemodynamic investigation. No extraction was identified across the lungs as evaluated by the same concentration of ANP in pulmonary and femoral arteries ( n = 7). The concentration of ANP in a superficial arm vein relative to the femoral artery varied considerably and extractions from 0% up to 58% were identified (mean 18%). The results suggest a high degree of, but only to some extent selective, extraction of ANP, which may account for its proposed short plasma half‐life. Due to the different concentrations of ANP in various vascular beds, sampling site should be thoroughly specified.
ABSTRACT— Endogenous α‐atrial natriuretic peptide (ANP) in plasma is elevated in various hypervolaemic conditions. Possible relationships between circulating immunoreactive ANP and cardiovascular and splanchnic haemodynamics were therefore studied in patients with cirrhosis (n = 16) and controls (n = 12). Arterial plasma concentration of ANP in supine patients was (mean ± SEM) 33 ± 4 vs 41 ± 10 pg/ml (9.9 ± 1.2 vs 12.3 ± 3.0 fmol/l) in controls (n.s.), and there was a weak direct correlation with right atrial pressure (r = 0.36, P = 0.05). There was no relationship with the presence of ascites or diuretic treatment. Central blood volume (CBV, i.e. the blood volume in the heart cavities, lungs, and aorta), determined from the mean transit time of 125 I‐labelled albumin and cardiac output, was significantly reduced in cirrhotics compared to controls (1.45 ± 0.12 vs. 1.83 ± 0.10 1, P < 0.02) and inversely correlated with portal pressure (r = –0.42, P < 0.05), whereas total plasma volume was somewhat increased (3.51 ± 0.2 vs 3.19 ± 0.2, 0.05 < P < 0.1). A high arterio‐venous extraction of ANP was found in the splanchnic system (extraction ratio 0.44 vs 0.28), kidney (0.45 vs 0.54), lower limb (0.53 vs 0.40), and forearm (0.27 vs 0.18) in patients and controls, respectively (n.s.). Our results suggest that the lack of elevation of circulating ANP in cirrhosis, even in the presence of actual fluid retention, may be explained by central hypovolaemia in these patients. Turnover and degradation of ANP is rapid and normal, as evaluated from the tissue extraction ratios.
The influence of plasma sodium concentration in the control of sodium excretion was investigated in conscious, water‐diuretic dogs. NaCl was infused for 60 min as a hypertonic or isotonic solution at a rate of 60 μmol NaCl min ‐1 kg ‐1 body wt. Plasma sodium concentration rose only during hypertonic infusion ( P < 0.05). Sodium excretion increased markedly with both infusions (hypertonic, from 2.4 ± 0.6 to 105 ± 27μmol min ‐1 ; isotonic, from 3.9 ± 1.3 to 58 ± 17 μmol min ‐1 ). Fractional sodium excretion increased more during hypertonic than during isotonic infusion. Hypertonic infusion decreased diuresis from 3.1 ± 0.5 to 1.3 ± 0.6 ml rnin ‐l , while isotonic infusion elicited an increase from 3.9 ± 0.5 to 7.2 ± 0.7 ml min ‐1 . Plasma renin activity and plasma aldosterone decreased markedly in both series ( P < 0.05), the relative changes in the two series being very similar. Central venous pressure increased (2.8 ± 0.7 to 4.5 ± 1.0 mmHg) during isotonic infusion but not significantly during hypertonic infusion. Arterial pressure, heart rate and plasma levels of atrial natriuretic peptide and catecholamines did not change measurably in either series. It is concluded that simultaneous increases in extracellular volume and sodium concentration cause a larger natriuretic response than a change in volume alone, and that a 40–fold increase in sodium excretion may occur without measurable changes in plasma atrial natriuretic peptide concentration.
The renal responses to 120-min infusions of arginine vasopressin (AVP) were investigated in healthy volunteers undergoing water diuresis induced by an oral water load of 20 ml/kg body wt. AVP at 1 pg.min-1.kg-1 (approximately 10(-15) mol.min-1.kg-1) decreased urine flow (12.2 +/- 1.7 to 7.4 +/- 1.5 ml/min) and free water clearance (9.7 +/- 1.5 to 4.8 +/- 1.4 ml/min) and increased urine osmolality (Uosmol; 71 +/- 6 to 115 +/- 15 mosmol/kgH2O); 5 pg.min-1.kg-1 elicited pronounced antidiuresis (14.4 +/- 0.9 to 0.9 +/- 0.3 ml/min) with maximal Uosmol of 621 +/- 95 mosmol/kg. In response to 25 pg.min-1.kg-1, maximal Uosmol was 869 +/- 38 mosmol/kg. Responses developed gradually and stabilized within the 2nd h of infusion. AVP at 1 and 5 pg.min-1.kg-1 was without effect for at least 20 min. Only 25 pg.min-1.kg-1 caused a significant rise in plasma AVP (1.2 +/- 0.2-2.0 +/- 0.1 pg/ml), and with this dose sodium excretion decreased. The rates of K+ excretion, as well as plasma aldosterone and atrial natriuretic peptide concentrations, were unaffected by AVP. It is concluded that the human kidney is sensitive to changes in the rate of secretion of AVP of less than 1 pg.min-1.kg-1 and that the maximal change occurs after 1-2 h of constant infusion. It is estimated that the rate of infusion of AVP required to produce isosmolar urine during overhydration is approximately 3 pg.min-1.kg-1.
