Dschietzig and colleagues showed higher coronary sinus than left ventricular relaxin concentrations in 11 of 14 patients with severe CHF, suggesting that the failing heart may be a source of circulating relaxin.3
We found the opposite across the non-failing heart—that is, net extraction of relaxin. Further inspection of the data from Dschietzig and colleagues shows no transcardiac gradient in patients with moderate CHF and an aorta–coronary sinus decrement in controls, in keeping with our findings.3
This suggests that the contribution of the heart to circulating relaxin varies according to the presence or absence of CHF. Whether it is left ventricular systolic dysfunction, abnormal pulmonary or systemic haemodynamics, neurohumoral activation or other factors that leads to net cardiac secretion of relaxin in CHF is presently unknown.
The pattern of relaxin secretion/extraction is distinct from other hormones. A type and B type natriuretic peptide increase from aorta to coronary sinus in both the non-failing and failing heart (more notably in the latter).4
Adrenomedullin is also secreted by both the failing and non-failing heart. In contrast, endothelin-1 is extracted by the failing heart, whereas there seems to be either no transcardiac gradient or higher coronary sinus concentrations in non-failing hearts.5
There is no transcardiac gradient in plasma aldosterone concentration in the non-failing heart but an increment in coronary sinus aldosterone concentration in CHF.
Interpretation of the cardiac extraction of relaxin by the normal heart, compared to its secretion by the failing heart, is difficult. The mechanisms of relaxin clearance from the circulation are unknown. Changes in the transcardiac concentration of other peptides seem to reflect changes in receptor density/affinity—for example, decreases in endothelin concentration across the failing heart are probably caused by the increase in myocardial ETA
The receptors for relaxin have only recently been described and nothing is known about the effect of CHF on their expression.1
The transpulmonary gradient in relaxin concentration has not been described before. Neither net extraction nor secretion occurred, which is different than for other peptides. Pulmonary extraction of A type natriuretic peptide4
and adrenomedullin has been described. For endothelin, some have described no transpulmonary concentration gradient, others pulmonary extraction, and others still that both secretion and extraction, which balance each other out, occur.5
Relaxin also differs from other peptides in having no effect in small pulmonary resistance arteries (whereas it is a potent vasodilator in comparable vessels from the systemic circulation).2
In summary, in patients with coronary disease but without CHF, there is net cardiac extraction of relaxin in contrast to reported secretion in CHF. In patients without CHF there is no transpulmonary gradient in relaxin.