Elevated plasma atrial natriuretic peptide (ANP) levels and concomitant increases in renal sodium and water excretion are often encountered in respiratory diseases associated with increased airway resistance such as obstructive sleep apnea. The present study utilized an anesthetized rat model to determine the principal mechanism(s) responsible for stimulation of ANP release in this clinical syndrome. A 10-minute increase in external resistive loading, which reduced peak tracheal pressure to −15 to −17 mm Hg produced a significant increase in both central venous pressure and right atrial transmural pressure. This maneuver subsequently resulted in significant transient increases in glomerular filtration rate; urine flow; urinary Na+, K+, and Cl− excretion; and urinary cyclic guanosine monophosphate (cGMP) excretion, which was taken as an index of increased circulating levels of ANP. Similar changes in renal function and cGMP excretion occurred when arterial PO2 was lowered to a degree equivalent to that seen with increased resistive loading. Lowering arterial PO2 also significantly increased mean central venous pressure and right atrial transmural pressure. Conversely, the resistive loading-induced changes in renal function and cGMP excretion did not occur when the reduction in arterial PO2 was prevented by breathing a high PO2 gas mixture during the resistive loading. Additionally, O2 supplementation prevented the increases in both mean central venous pressure and right atrial transmural pressure caused by increased resistive loading. These data indicate that the elevated ANP release that results from an acute increase in external resistive loading is not caused by a decrease in intrathoracic pressure but rather suggest that the elevated ANP release is primarily caused by an increased right atrial transmural pressure resulting from hypoxia-induced pulmonary vasoconstriction.

The aim of the present study was to determine whether bradykinin affects NaCl reabsorption in the medullary thick ascending limb of the loop of Henle. At 10−8 M, bradykinin significantly inhibited Cl− transport in the in vitro microperfused rat medullary thick ascending limb by 67% (P < 0.01). This inhibitory effect could be totally prevented by preincubating tubules with the bradykinin B2 receptor antagonist Nα-adamantaneacetyl-d-Arg-[Hyp3,Thi5,8,d-Phe7]bradykinin (10−6 M). In contrast, the bradykinin B1 receptor agonist des-Arg9 bradykinin (10−6 M) had no effect on Cl− transport. Bradykinin caused transient increases in intracellular Ca2+ concentration, which could be blocked by the bradykinin B2 receptor antagonist, but could not be reproduced with the bradykinin B1 receptor agonist. These data suggest that the natriuretic and diuretic effect of bradykinin in vivo is due, at least in part, to a bradykinin B2 receptor-mediated inhibition of NaCl reabsorption in the medullary thick ascending limb of the loop of Henle.

We have examined the effects of chronic gentamicin treatment on arginine8-vasopressin (AVP)-dependent cyclic AMP (cAMP) metabolism in rat medullary collecting tubules (oMCT) and medullary thick ascending limbs of Henle's loop (mTALH). Gentamicin attenuated AVP-stimulated cAMP accumulation to a greater extent in the mTALH (delta -51%) than in the oMCT (delta -25%). The mechanism of attenuation differed between segments, and could not be attributed to either direct inhibition of adenylate cyclase activity nor direct potentiation of cAMP-phosphodiesterase activity. These data suggest that the gentamicin-induced decrease in renal concentrating ability may be due at least in part to reduced AVP-dependent cAMP accumulation in the oMCT and mTALH.