38 research outputs found
Design and Structure--Activity Relationship of Novel Endothelin Receptor A Tripeptide Antagonists
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 minâ1) 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 minâ1) 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 mlâ1. ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics.Intrasplenic ANF (6.5 pmol minâ1) caused a sustained increase in intrasplenic fluid efflux from 0.1 ± 0.1 to 0.3 ± 0.1 ml minâ1, and in capillary filtration coefficient (Kf) from 1.2 ± 0.5 to 2.4 ± 0.6 ml mmHgâ1 minâ1 (100 g tissue)â1.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 minâ1).The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol minâ1) did not alter splenic intravascular pressure or pre-/post-capillary resistance.The ANF antagonist A71915 (8.3 and 83 pmol minâ1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), 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 NPRA