Left atrial distension and antiorthostatic decrease in arterial pressure and heart rate in humans

It was investigated to what degree left atrial distension augments the hypotensive effects of a 15-min moderate antiorthostatic maneuver in humans. Ten healthy males underwent a posture change from upright seated (Seat, legs horizontal) to supine (Sup) or to supine with simultaneous lower body negative pressure (Sup + LBNP) to keep left atrial diameter (LAD) unchanged. After 2.5 min of Sup, mean arterial pressure (MAP) decreased from 94 ± 3 to 86 ± 3 mmHg ( P < 0.05), whereas a similar decrease was delayed 7.5 min into Sup + LBNP. Heart rate (HR) decreased within 2.5 min of Sup from 68 ± 2 to 60 ± 3 beats/min ( P < 0.05) and remained significantly decreased for at least 2.5 min longer than during Sup + LBNP. Aortic systolic distension (ASD) increased by 59 ± 17% during Sup ( P < 0.05) but was unchanged during Sup + LBNP. The 29 ± 4% decrease in plasma norepinephrine (NE) during Sup ( P < 0.05) was abolished during Sup + LBNP. In conclusion, the increases in LAD and ASD seem important stimuli for the prompt decrease in MAP, the 2.5-min longer-lasting decrease in HR, and the sustained decrease in NE during a 15-min moderate antiorthostatic posture change in humans.

Control of atrial natriuretic factor by right and left atrial distension in pregnant sheep

Previous studies of the atrial stretch-atrial natriuretic factor (ANF) relationship during pregnancy have employed volume expansion and measured only right atrial pressure (RAP). Consequently, we studied nonpregnant (n = 7) and 115- to 125-day pregnant (n = 7) sheep and assessed the ANF response to changes of RAP and left atrial pressure (LAP) induced by graded balloon inflation. Ewes prepared with vascular catheters and atrial balloons were studied after recovery from preparatory surgical procedures. The basal levels of mean arterial pressure (MAP, 83 +/- 3 mmHg), RAP (2.1 +/- 0.7 mmHg), LAP (4.7 +/- 0.9 mmHg), and heart rate (HR, 102 +/- 6 beats/min) were similar in nonpregnant and pregnant sheep. Pregnancy also resulted in elevation of ANF concentration from 25 +/- 6 to 57 +/- 4 fmol/ml. With right atrial distension, the RAP-ANF relationships were similar in both nonpregnant and pregnant sheep, with a 10-mmHg increase in RAP increasing ANF by an average of 95 +/- 9 fmol/ml. In nonpregnant sheep, the LAP-ANF relationship was more responsive than RAP-ANF because a 10-mmHg increase in LAP resulted in a 193 +/- 10 fmol/ml increase in ANF. Moreover, during pregnancy, the LAP-ANF relationship was significantly more sensitive because a 10-mmHg increase in LAP resulted in a 433 +/- 15 fmol/ml elevation of ANF. These data demonstrate that plasma ANF levels are more responsive to distension of the left atria than to the right. More importantly, the ANF response to left, but not right, atrial distension is enhanced by pregnancy.

Cardiac-renal-neural reflex plays a major role in natriuresis induced by left atrial distension

The role of cardiac-renal-neural reflex in the natriuresis induced by left atrial balloon inflation was investigated in conscious dogs. Female mongrel dogs were assigned randomly to 1) sham-operated (n = 8), 2) cardiac-denervated (n = 6), and 3) renal-denervated (n = 8) groups. The dogs were chronically instrumented with a bipolar stainless steel wire electrode for measurement of renal sympathetic nerve activity (RSNA). Balloon inflation induced a step increase in left atrial pressure (Pla) by 7.7 +/- 1.7 mmHg, a step decrease in RSNA (-66.6 +/- 5.5%), and concomitant increases in urine flow (441 +/- 142%), osmolal excretion (60 +/- 12%), and sodium excretion (300 +/- 69%) in sham-operated dogs. Renal denervation abolished the diuresis and natriuresis during balloon inflation. Chronic cardiac denervation abolished also the diuresis and natriuresis in the face of a similar increase in Pla. RSNA did not change significantly throughout the experimental period in cardiac-denervated dogs. It is concluded that a sustained reduction of RSNA originating from left atrial mechanoreceptors plays a major role in the natriuresis during left atrial distension in conscious dogs.

Evidence that urodilatin, rather than ANP, regulates renal sodium excretion.

Urodilatin, a closely related member of the atrial peptide family, was discovered recently in human urine. Urodilatin (ANP 95-126) is believed to be produced within the kidney and is natriuretic; evidence indicates that most of the ANP-like immunoreactivity in the kidney elutes with urodilatin rather than with ANP. Moreover, urodilatin is little affected by renal enzymes that inactivate atriopeptin. To determine the relative importance of urodilatin versus ANP in the regulation of renal sodium excretion, we studied intact and cardiac-denervated conscious dogs under three experimental conditions: (1) spontaneous sodium excretion, (2) intravenous infusion of saline, and (3) left atrial distension. Urodilatin was measured in urine with a newly developed radioimmunoassay that selectively measures urodilatin without any cross-reactivity with alpha-human atrial natriuretic peptide (alpha-hANP); alpha-hANP was measured in plasma by radio-immunoassay because it is rapidly inactivated in the kidney by enzymatic activity. In each group of experiments, sodium excretion correlated better with urodilatin than it did with circulating alpha-hANP. The correlation coefficient (r value) between urodilatin excretion and renal sodium excretion exceeded 0.8 in 13 of 18 experiments and was below 0.6 in only 2 experiments. On the other hand, the correlation between circulating atriopeptin and sodium excretion exceeded 0.8 in only 3 of 18 experiments and was below 0.6 in 10 experiments. A negative correlation between plasma atriopeptin and renal sodium excretion was observed during left atrial distension in the cardiac-denervated dogs. These results and other considerations suggest that urodilatin, rather than atriopeptin, is the member of the ANP family that is primarily involved in the regulation of renal sodium excretion.

Natriuresis during atrial distension and a concurrent decline in plasma atriopeptin

In the conscious dog, left atrial distension elicits a composite response that modulates both cardiovascular and renal function. The response to atrial distension may be mediated by the combined effects of neural reflexes and the release of atriopeptin. To assess the relative contributions of atrial reflex mechanisms and circulating atriopeptin to the renal response elicited by atrial distension, alpha-human atrial natriuretic peptide (alpha-hANP) was infused into conscious dogs at 50 ng.kg-1.min-1 for 60 min. Then the infusion was stopped abruptly, and left atrial pressure was increased 8 mmHg by inflating a balloon positioned above the mitral valve. Plasma atriopeptin decreased during the 40-min period of atrial distension, but urine flow and sodium excretion increased during this time. In another series of experiments, volume expansion was substituted for atrial distension. Saline (24 ml/kg) was infused intravenously for 5 min immediately after the 60-min period of alpha-hANP infusion. Urine flow and sodium excretion increased after administration of saline even though plasma atriopeptin decreased substantially during the same time period. These results provide evidence that circulating levels of atriopeptin do not play a dominant role in influencing sodium excretion either during atrial distension or in response to saline infusion.

Effects of atriopeptin infusion versus effects of left atrial stretch in awake dogs

We infused synthetic atriopeptin III intravenously into 10 conscious dogs while monitoring renal function and systemic hemodynamics. The results obtained from these infusion experiments were compared with results from other experiments in which left atrial distension was performed in the same dogs. Both atriopeptin infusion and left atrial distension caused significant increases in urine flow, sodium excretion, potassium excretion, and free water reabsorption and a significant decrease in renal blood flow. On the other hand, the pattern of systemic hemodynamic responses to atriopeptin infusion were quite different from the hemodynamic responses elicited by left atrial distension. However, there was a striking concordance between the renal effects of atriopeptin and those of left atrial distension. We therefore hypothesize that the renal response to left atrial distension in the conscious dog is mediated largely by the release of natriuretic peptides from the atria.

Time course of changes in plasma vasopressin during atrial distension

Distension of the left atrium in chloralose anaesthetized dogs causes a diuresis and dilution of the urine. It has been reported previously that if distension of the atrium is maintained then urine flow reaches a peak after 50 min and then declines. A radioimmunoassay was used to measure plasma arginine vasopressin (AVP) at 10-min intervals before, during, and after atrial distension for 90 min. Plasma AVP decreased during atrial distension and did not increase until after the atrial distension was removed.Urine volume and free-water clearance increased and urine osmolality decreased, to reach maximum changes after 50 min. Although there was then a decline in some experiments, after reaching the peak changes, the mean values of the group did not show any statistically significant decline. Thus the urinary changes were also present for the 90 min of left atrial distension. The results are consistent with the hypothesis that the.diuretic response to left atrial distension is dependent upon decreased release of AVP from the neurohypophysis.