Renin Secretion by the Spontaneously Diabetic Rat

Abstract

Renal function studies and measurements of in vivo plasma renin activity (PRA), kidney renin content, and renin secretion by isolated, perfused kidneys were performed in spontaneously diabetic and nondiabetic BioBreeding/Worcester (BB/W) rats. Diabetic animals evidenced hyperglycemia, glycosuria, and plasma volume expansion. After dietary sodium deprivation, plasma volume fell to levels equivalent to those of sodium-deprived, nondiabetic rats. Dietary sodium deprivation evoked a larger proportional increase in PRA among diabetic than nondiabetic animals, although PRA before sodium restriction was equivalent in the two groups. Basal renin release (RR) was higher from isolated, perfused kidneys from diabetic rats than from nondiabetic kidneys. Diabetic kidneys, moreover, displayed increased kidney renin content (KRC). By contrast, while isoproterenol (10(-5) M) stimulated a nearly fivefold increment in RR from nondiabetic, perfused kidneys, a negligible effect was observed in diabetic kidneys. The dose-response curve of renin secretion (as a proportion of total renal content) in response to isoproterenol was shifted downward. Hence, while KRC and spontaneous RR by isolated, perfused kidneys were increased, the increment in PRA with salt depletion and the renin-secretory response to isoproterenol in vitro were impaired. We propose that specific defects in renin secretion, in particular, the response to beta-adrenergic stimulation, may be operative in diabetes.

Influence of fluvastatin on cardiac function and baroreflex sensitivity in diabetic rats

“…Interestingly, the increase of ΔHR/ΔMABP, an indicator of BRS, was greater in DM rats compared with Ctr rats in response to PE and SNP injections. This result is not consistent with those of some DM models, which may be largely attributed to the different time course of development for diabetes (ie, 12, 24, and 48 weeks): metabolic disorders caused by a hyperglycemic state or insulinopenia may be related to time-dependent changes in parasympathetic and sympathetic control [25,26] and different osmotic diuresis after the DM model was established [27,28] . In addition, discrepancies in species, experimental design and diabetic inducer may also affect the results to some extent [29,30] .…”

Effects of exercise training on autonomic and myocardial dysfunction in streptozotocin-diabetic rats

“…Jackson and Carrier (16) suggested that the decrease in AP may be the result of a decreased cardiac output in diabetic sedentary rats due to hypovolemia caused by hyperglycemic osmotic diuresis. However, Cohen et al (17) observed that these animals were polyuric with a high urine flow, reflecting the osmotic diuretic effects of glucose. The hypotension observed in the sedentary diabetic group may also have been due to an increase in parasympathetic outflow, although Maeda et al (2) and the present data demonstrated a decrease in vagal function, suggesting that changes in AP are not related to an increase in parasympathetic outflow.…”

Baroreflex and chemoreflex dysfunction in streptozotocin-diabetic rats

“…Jackson and Carrier (1) suggested that the decrease in AP may be the result of a decreased cardiac output in diabetic rats due to hypovolemia caused by hyperglycemic osmotic diuresis. However, Cohen et al (13) observed that the diabetic animals were polyuric with a high urine flow, reflecting the osmotic diuretic effect of glucose. In these experiments, the renal physiologic parameters demonstrated increased plasma volume, presumably related to osmotic effects of glucose resulting in both expansion of extracellular fluid volume and induction of diuresis (13).…”

“…However, Cohen et al (13) observed that the diabetic animals were polyuric with a high urine flow, reflecting the osmotic diuretic effect of glucose. In these experiments, the renal physiologic parameters demonstrated increased plasma volume, presumably related to osmotic effects of glucose resulting in both expansion of extracellular fluid volume and induction of diuresis (13). In the present study, the collection of blood samples may have contributed to the changes in AP, although the rats were injected with equal volumes of saline after collection.…”

“…The controversial data regarding changes in baroreflex sensitivity after diabetes may be attributed to differences in the experimental design as well as in the analytical methodology (5,12), suggesting that these differences may be correlated with the time course of diabetes. Indeed, not only the volume status of rats but also factors other than plasma volume may be altered during diabetes (13) and, consequently, the osmotic diuresis may be different at each time after STZ injection. Moreover, the animal model and the diabetogen used could change the interpretation of the data (6).…”