Plasma renin activity (PRA) and inactive renin(IR, activated by trypsin) were measured in the plasma of 15 type II diabetics with autonomic neuropathy (group 3), 15 type II diabetics without (group 2), and 14 nondiabetic control subjects (group 1) in the recumbent position. There were no significant differences between the 3 groups with respect to age, ideal body weight, supine resting mean blood pressure, serum creatinine, daily urinary excretion of sodium, or renin substrate at the time of study. Autonomic neuropathy (AN) was assessed by measurement of the ratio of the longest to the shortest R-R interval during deep breathing (E/I-ratio) and by postural hypotension. PRA was significantly lower in group 3 than in group 1 (p less than 0.05). The IR level was significantly higher in group 3 than in groups 2 and 1 (p less than 0.005 for both comparisons). The ratio of active renin to total renin (TR) (PRA/(IR + PRA)) was significantly lower in group 3 than in groups 2 and 1 (p less than 0.001 for both comparisons). The IR level and PRA/(IR + PRA) were significantly correlated with E/I-ratio (r = -0.498, p less than 0.01 and r = 0.588, p less than 0.001, respectively) and with the severity of postural hypotension (r = 0.383, p less than 0.05 and r = 0.401, p less than 0.05, respectively), but not with the daily urinary excretion of protein or 24 h-creatinine clearance (24 h-Ccr) in the whole diabetics. From these results, we conclude that autonomic neuropathy might be a more important factor than nephropathy in the lower PRA and higher IR level in type II diabetics with AN.

No abstract

A variety of abnormality has been reported in the cation transport systems in erythrocytes in essential hypertension. To determine the existence of similar abnormality in diabetics with hypertension, sodium (Na+) influx into erythrocytes in the presence of ouabain (measured by using 22Na+), and the Na+ and potassium (K+) content in intact erythrocytes were examined. Subjects, all of whom were Japanese, were divided into 4 groups; 23 nondiabetic, normotensive control subjects without family history of hypertension (control group), 20 patients with essential hypertension (group 1), 21 normotensive diabetics without family history of hypertension (group 2) and 15 hypertensive diabetics (group 3). Na+-K+ pump activity (measured by using 86Rb+) was studied in some of them, too. Na+ influx in group 1 was 0.451 +/- 0.111 m mol/Kg erythrocytes/h, significantly more elevated than that in the control group (0.345 +/- 0.080, p less than 0.001). Na+ influx in group 2 (0.435 +/- 0.094) was significantly greater than that in the control group (p less than 0.005), but no significant difference was found between groups 1 and 2. Na+ influx in group 3 (0.551 +/- 0.128) was significantly higher than that in the control group (p less than 0.001), in group 1 (p less than 0.02), or in group 2 (p less than 0.005). There were no significant differences in Na+-K+ pump activity, or Na+ and K+ content among the 4 groups. These findings suggested that: Na+ influx into ouabain-treated erythrocytes was higher in patients with essential hypertension than in control subjects in Japanese, diabetes mellitus per se might increase Na+ influx, and the elevation of blood pressure in hypertensive diabetics as well as in essential hypertensives might be related to the increased Na+ influx.

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: 260 mg/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 2 h, 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 2 min, 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 240 min after the pedicle occlusion in the different groups of rats. The renal blood levels of PAC increased by more than three times at 240 min compared to the control values, while PIC decreased to one third of the control values. PTC increased at 120 and 240 min. Renal tissue levels of renin were also measured at 0 and 120 min 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: 11.3 mg/100g) for 2 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

To determine the role of the kallikrein-kinin (KK) system in patients with diabetes mellitus in relation to nephropathy and/or hypertension, the single-dose effects of captopril (25 mg, p.o.) were examined in 9 control subjects and 32 diabetics (group 1; 11 normotensives without nephropathy, group 2;10 hypertensives without nephropathy, group 3; 11 hypertensives with nephropathy). Significant hypotensive effects of captopril were found in groups 1 and 2 as well as in the control group, but not in group 3. These hypotensive effects were completely blocked by the infusion of ethyl-p-(6-guanidinohexanoyloxy) benzoate methanesulfonate (FOY), a kallikrein inhibitor. The administration of captopril during vehicle infusion induced a significant elevation of plasma renin activity (PRA) at 60 and 120 min after captopril in each group, except for group 3. FOY cancelled these captopril-induced effects on PRA in those groups. No correlation was found between pretreatment PRA and the changes in mean blood pressure (MBP) after captopril during vehicle infusion in whole diabetics. In addition, the daily urinary excretion of kallikrein in group 3 was significantly lower than that in groups 1 and 2 as well as in the control group. These results suggest that the hypotensive action of captopril in diabetics without nephropathy may be largely due to activating the KK system, and that the KK system may be suppressed in hypertensive diabetics with nephropathy.