Atrial natriuretic factor increases splenic microvascular pressure and fluid extravasation in the rat

The spleen is an important site of atrial natriuretic factor (ANF)‐induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood‐perfused (1 ml min −1 ) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1‐28), infused into the splenic artery of anaesthetized male rats, caused a dose‐dependent (0.3‐59 pmol min −1 ) increase in microvascular pressure from 11.3 ± 0.7 to 14.9 ± 0.5 mmHg and in post‐capillary resistance from 7.2 ± 0.6 to 10.1 ± 1.1 mmHg ml −1 . ANF elicited no change in splenic pre‐capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min −1 ) caused a sustained increase in intrasplenic fluid efflux from 0.1 ± 0.1 to 0.3 ± 0.1 ml min −1 , and in capillary filtration coefficient ( K f ) from 1.2 ± 0.5 to 2.4 ± 0.6 ml mmHg −1 min −1 (100 g tissue) −1 . Mechanical elevation of splenic intravascular pressure (from 11.3 ± 0.7 to 22.4 ± 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 ± 0.3 to 1.4 ± 0.3 ml min −1 ). The natriuretic peptide receptor‐C (NPR C )‐specific agonist C‐ANF(4‐23) (12.5 and 125 pmol min −1 ) did not alter splenic intravascular pressure or pre‐/post‐capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min −1 ), which blocks ANF‐stimulated cGMP production via natriuretic peptide receptor‐A (NPR A ), inhibited the ANF‐induced changes in splenic microvascular pressure and post‐capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post‐capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPR A .