Permeability and contractile responses of collecting lymphatic vessels elicited by atrial and brain natriuretic peptides

Key points•  Atrial and brain natriuretic peptides (ANP and BNP, respectively) are hormones released into the bloodstream when heart muscle is stretched (e.g. zero‐gravity, hypertension, congestive heart failure) and serve to reduce the blood volume. •  One way that these peptides relieve blood volume is to increase the permeability of the smallest blood vessels, facilitating fluid and protein distribution into the tissue spaces. •  Whether these peptides target lymphatic vessel function to participate in fluid distribution is currently unknown. •  ANP and BNP (100 n m ) both elicited significant increases in lymphatic vessel permeability, but altered contractile function differentially in vivo.•  A likely consequence is that more fluid leaks from the lymphatics into the tissues, which represents a novel compensation for volume overload. This work demonstrates for the first time that lymphatic vessel permeability can be regulated in vivo .Abstract  Atrial and brain natriuretic peptides (ANP and BNP, respectively) are cardiac hormones released into the bloodstream in response to hypervolaemia or fluid shifts to the central circulation. The actions of both peptides include natriuresis and diuresis, a decrease in systemic blood pressure, and inhibition of the renin–angiotensin–aldosterone system. Further, ANP and BNP elicit increases in blood microvessel permeability sufficient to cause protein and fluid extravasation into the interstitium to reduce the vascular volume. Given the importance of the lymphatic vasculature in maintaining fluid balance, we tested the hypothesis that ANP or BNP (100 n m ) would likewise elevate lymphatic permeability ( P s ) to serum albumin. Using a microfluorometric technique adapted to in vivo lymphatic vessels, we determined that rat mesenteric collecting lymphatic P s to rat serum albumin increased by 2.0 ± 0.4‐fold ( P = 0.01, n = 7) and 2.7 ± 0.8‐fold ( P = 0.07, n = 7) with ANP and BNP, respectively. In addition to measuring P s responses, we observed changes in spontaneous contraction amplitude and frequency from the albumin flux tracings in vivo . Notably, ANP abolished spontaneous contraction amplitude ( P = 0.005) and frequency ( P = 0.006), while BNP augmented both parameters by ∼2‐fold ( P < 0.01 each). These effects of ANP and BNP on contractile function were examined further by using an in vitro assay. In aggregate, these data support the theory that an increase in collecting lymphatic permeability opposes the absorptive function of the lymphatic capillaries , and aids in the retention of protein and fluid in the interstitial space to counteract volume expansion.