Alterations in rat renal cortical and medullary guanosine 3'5'-monophosphate accumulation by oxygen- and calcium-dependent and -independent mechanisms: evidence for a calcium-independent action of oxygen in renal inner medulla.

Factors influencing guanosine 3'5'-monophosphate (cGMP) metabolism were examined in slices of rat renal cortex, outer medulla, and inner medulla. In the presence of extracellular Ca2+ and O2, a gradation of steady-state cGMP levels was evident among the tissues (inner medulla greater than outer medulla greater than cortex). Carbamylcholine, bradykinin, histamine, and the divalent cation ionophore A23187 significantly increased cGMP in each tissue. The cGMP-stimulating action of these agents was reversibly abolished by exclusion of either Ca2+ or O2. The influence of Ca2+ and O2 on expression of effects of carbamylcholine and related cGMP agonists was interdependent in each region of the kidney, since both were required for expression of agonist action. By contrast, nitrite, nitroprusside, NH2OH, and nitrosoguanidine increased cGMP in the presence or absence of Ca2+ or O2. Thus, at least two distinct mechanisms for altering cGMP accumulation are operative or expressible in each region of the kidney: one that requires and one that does not require the presence of extracellular Ca2+ and O2. Results also suggested a role for transmembrane transport of Ca2+ in the maintenance of basal cGMP and in the expression of the responses to Ca2+-dependent agonists in renal cortex, outer and inner medulla. Thus, verapamil, which can block such transport, lowered basal cGMP and abolished these responses while ionophore A23187 enhanced cGMP in cortex and medulla only in the presence of Ca2+. The interrelationship of Ca2+ and O2 in control of basal cGMP levels clearly differed in cortex compared to inner medulla. In cortex, Ca2+ and/or O2 deprivation produced quantitatively similar reductions in cGMP. Moreover, expression of the action of O2 to increase cortical cGMP required Ca2+. Thus, O2 effects on cGMP in cortex were closely coupled with or mediated through Ca2+. By contrast, in inner medulla, O2 deprivation resulted in more pronounced reduction in basal cGMP than did Ca2+-deprivation, and O2 significantly increased inner medullary cGMP in the absence of extracellular Ca2+...