Atrial natriuretic peptides in canine hypoxic pulmonary vasoconstriction.

STUDY OBJECTIVE: The aim of the study was to investigate whether atrial natriuretic peptides have a physiological role in regulation of the pulmonary circulation. DESIGN: Plasma concentrations of immunoreactive atrial natriuretic peptide and guanosine-3',5'-cyclic monophosphate (cGMP) were measured during evaluation of pulmonary vascular tone by multipoint pulmonary arterial pressure-cardiac index (Ppa/Q) relationships. SUBJECTS: Experimental animals were 17 mongrel dogs of either sex, 21-35 kg weight, anaesthetised with pentobarbitone. MEASUREMENTS AND MAIN RESULTS: Measurements of Ppa/Q relationships and atrial natriuretic peptide/cGMP were made during hyperoxia (Fio2 0.4) and hypoxia (Fio2 0.1). Hypoxic pulmonary vasoconstriction, defined as hypoxia induced increase in pulmonary artery pressure over the entire range of Q studied from 2-5 litre.min-1.m-2, was elicited in nine dogs ("responders"). In the other eight dogs, hypoxia did not change pulmonary artery pressure over the entire range of Q studied ("non-responders"). At neither the highest nor the lowest Q in hyperoxia did atrial natriuretic peptide and cGMP concentrations differ between these two groups, nor did acute reduction in Q affect the concentrations in either group. At the highest Q, plasma atrial natriuretic peptide increased in hypoxia from 11(SEM 2) to 15(3) pmol.litre-1 in the responders (p less than 0.05), and from 15(2) to 20(2) pmol.litre-1 in the non-responders (p less than 0.05). However at the lowest Q, atrial natriuretic peptide was increased in non-responders only, from 17(3) to 23(4) pmol.litre-1 (p less than 0.05). CGMP did not vary significantly in any experimental condition. CONCLUSIONS: Hypoxia slightly increased plasma atrial natriuretic peptides without any relationship with associated pulmonary haemodynamic changes. These data do not support the hypothesis that atrial natriuretic peptides play a physiological role in the regulation of the pulmonary circulation in dogs.

Pharmacological doses of atrial natriuretic factor do not inhibit canine hypoxic pulmonary vasoconstriction.

It has been recently suggested that atrial natriuretic factor (ANF) might be involved in the physiological regulation of pulmonary circulation. Therefore, we investigated the pulmonary hemodynamic response to 20-min infusions of 0.05, 0.1, and 0.2 micrograms kg-1 min-1 of alpha human ANF in five dogs alternatively ventilated with hyperoxic (FIO2 0.4) and hypoxic (FIO2 0.1) gas mixtures. Cardiac output was held constant by the inflation of a balloon in the inferior vena cava or by opening of an arteriovenous femoral fistula, in order to discriminate between active and passive changes in pulmonary arterial pressure (Ppa). Hypoxia increased Ppa from 14 +/- 3 to 24 +/- 3 mm Hg (mean +/- SE, p less than 001). Circulating ANF and guanosine 3',5'-cyclic monophosphate (cGMP) were increased to 1,326 +/- 299 pmol L-1 (normal is less than 10 pmol L-1) and 75.5 +/- 5.8 pmol ml-1 (normal is less than 15 pmol ml-1) respectively, at the highest infused dose. After ANF infusion, heart rate (HR), Ppa, pulmonary capillary wedge pressure (Ppw), and right atrial pressure (Pra) did not change either in hyperoxia or hypoxia. Systemic arterial pressure (Psa) decreased after ANF, but only in hypoxia. Thus, ANF at pharmacological doses associated with a 100-150-fold increase in plasma levels proved to be a poor vasodilator and, in particular, did not inhibit hypoxic pulmonary vasoconstriction (HPV). These results do not support the speculation that ANF might be an endogenous vasodilating modulator of pulmonary vascular tone in the dog.

Natriuresis and atrial natriuretic factor secretion during inappropriate antidiuresis.

The mechanisms responsible for the natriuresis encountered in the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are not fully understood. The present study explores the role of atrial natriuretic factor (ANF). Eight subjects unable to excrete ingested free water normally (three patients with SIADH and five healthy humans after intranasal administration of desmopressin) underwent a standard oral water loading test. Plasma ANF level and urinary sodium excretion increased during water retention, whereas plasma aldosterone value decreased later. The increment of urinary sodium excretion rate was significantly correlated with that of plasma ANF. In two patients with hyponatremia due to SIADH, plasma ANF levels were increased during the hyponatremic phase of their condition and decreased under water restriction. In one of them, marked natriuresis was observed when the plasma ANF level was high. It is concluded that secretion of ANF is acutely and chronically stimulated during water retention in SIADH and that ANF may be in part responsible for the natriuresis encountered in inappropriate antidiuresis.

Bartter's syndrome with a salt reabsorption defect in the cortical part of Henle's loop.

The pathogenesis of Bartter's syndrome remains uncertain. The prevailing theory postulates a defect in salt reabsorption, more frequently described in the thick ascending limb of Henle's loop. The patient we studied presents a normal urinary concentration capacity associated with impaired dilution, a free water clearance at the lower end of normal (5.4 ml/min/100 ml glomerular filtrate), a decreased distal fractional chloride reabsorption (54%) when studied during hypotonic saline diuresis, and a normal decrease in free water clearance after furosemide (2.1 ml/min/100 ml glomerular filtrate), suggesting a defect in the cortical part of Henle's loop. When studied during oral water diuresis, the fractional chloride reabsorption was normal (82%). This could be explained by a relative inability of the cortical diluting segment to reach maximal absorptive rates for NaCl. An inappropriate kaliuria related to an excessive delivery of salt load to the distal tubule is suggested by the correlation between urinary potassium and chloride excretion (r = 0.84; p less than 0.001). Aldosterone secretion participates also partially in the urinary potassium loss.