Mechanisms of hypoxia-induced atrial natriuretic factor release from rat hearts

Abstract

Potential mechanisms of hypoxia-induced atrial natriuretic factor (ANF) release [A.J. Baertschi, J.M. Adams, and M.P. Sullivan. Am. J. Physiol. 255 (Heart Circ. Physiol. 24): H295-H300, 1988] were investigated in Langendorff-perfused rat hearts. The ANF release was graded with stimulus intensity; 10 min of perfusion with Krebs-Henseleit solution equilibrated with 95, 20, 10, 5, and 0% oxygen led to peak ANF levels of 140 +/- 31 (SE), 202 +/- 20, 407 +/- 76, 659 +/- 119, and 516 +/- 83% of base-line ANF (159 +/- 14 pg/ml), respectively. Hypoxia-induced release of lactate dehydrogenase and creatine kinase did not correlate with ANF release; this finding, along with other experiments, rules out tissue damage as a significant factor. Phentolamine (1.3 microM) and propranolol (0.1 microM) each reduced peak hypoxia-induced (0% O2) ANF release to 333 and 310%, respectively, whereas atropine sulfate (15 microM) had no inhibitory effect. The three antagonists combined reduced the peak hypoxia-induced ANF release to the same extent (307%) as either phentolamine or propranolol alone. Earlier (24 h) catecholamine depletion of rats with 100 mg/kg 6-hydroxydopamine also significantly reduced peak hypoxia-induced ANF release to 330%. Neither the reduction of the ANF secretory responses by these interventions nor the remaining ANF response could be attributed to changes in atrial mechanics. Therefore, these studies demonstrate that alpha- and beta-adrenergic stimulation is responsible for approximately half the hypoxia-induced ANF release from the isolated heart, whereas an as yet undefined mechanism accounts for the remainder of the response.