Roles of the Kidney in Activation and Release of Plasma Inactive Renin in the Rat

Plasma inactive as well as active renin is supposed to originate from the kidney, though there is little direct evidence. As we have previously reported (Sakanaka et al., Folia Endocrinol. Jap., 63: 961-977, 1987; Miyazaki et al., J. Hypertension 4 (Suppl 6): S453-S455, 1986; Miyazaki et al., J. Hypertension 6: 33-40, 1988), the submandibular gland, but not the kidney, is thought to play an crucial role in releasing plasma inactive renin in the rat. In the present acute studies, we attempted to elucidate the roles of the kidney in the release mechanisms of plasma inactive renin.Adult male rats maintained on a regular rat chow (Na: 260mg/100g) were uninephrectomized, and vessel clips were placed on the renal pedicles of the contralateral kidneys to make completely ischemic and non-filtered kidneys. In the first protocol, the renal pedicles were occluded for 2 h, followed by the removal of the vessel clips. During the occlusion for 2h, plasma active renin concentration (PAC) in the peripheral blood obtained from the femoral cannulae decreased, while plasma inactive renin concentration (PIC) along with plasma total renin concentration (PTC) increased as in the case of total nephrectomy, which supports our previous studies. Then, declipping resulted in the rapid rise in PAC with the peak values at 2min, which was followed by its gradual decrease with time during the experimental period (30 min). On the other hand, PIC decreased gradually toward control levels with no rise after declipping.In the second protocol, blood trapped in the kidney was collected through the renal venous cannulae at 0, 60, 120 and 240min after the pedicle occlusion in the different groups of rats. The renal blood levels of PAC increased by more than three times at 240min compared to the control values, while PIC decreased to one third of the control values. PTC increased at 120 and 240min. Renal tissue levels of renin were also measured at 0 and 120min in the second protocol in the kidneys of rats which were maintained on a regular rat chow. Inactive renin concentration increased, while active renin concentration decreased. These were compatible with the results obtained in plasma.In the last protocol, the second protocol was in part repeated in salt-depleted rats which were kept on a low salt diet (Na: 11.3mg/100g) for 2 weeks. In these rats, renin was measured in blood recovered from the occluded kidneys at 0 and 120 min. PIR decreased and PAR increased as was observed in the second protocol.Taken together, the present data may suggest that 1) PIR in peripheral blood of rats treated with both unilateral nephrectomy and contralateral renal pedicle occlusion (temporary total nephrectomy), is released from extrarenal sites, supporting the data of our previous experiments in bilaterally nephrectomized rats.2) Extrarenal inactive renin release is suppressed by the kidney, since recirculation of the kidney resulted in the decrease of the peripheral levels of inactive renin.3) The parallel increase in active renin and the parallel decrease in inactive renin in both plasma and kidney tissues indicates that ischemia does not stimulate kidney renin secretion and that the kidney does not release the inactive form of renin but activates plasma inactive renin into the active form.