Search

Low-protein (LP) feeding (6%) of rats results in renal hemodynamic changes that are abolished by converting enzyme and nonpeptide AT1 inhibitors, suggesting a role for intrarenal angiotensin II (ANG II). Dietary protein is a stimulus for the expression of renal renin mRNA in intact and partially nephrectomized rats. In the present study, LP increased renal renin immunoreactivity and renin mRNA as assessed by in situ hybridization and Northern blot analysis; whole kidney expression of angiotensinogen mRNA was unaltered. Whole kidney, cortical, and medullary ANG I-converting-enzyme (ACE) mRNA was also increased in LP vs. normal protein. The changes occurred despite a reduced protein synthetic rate (RNA-to-DNA ratio) in the kidney of LP, which did not change expression of renal glyceraldehyde-3-phosphate dehydrogenase mRNA. These studies show for the first time that LP diet increases the expression of renal renin and ACE mRNA in intact rats; these may be responsible for the renal hemodynamic changes of LP.

Angiotensin II and catecholamines interaction in short-term low protein feeding. Renal and systemic hemodynamic responses to an α-adrenergic agonist (norepinephrine, NE) and an α-adrenergic antagonist (phentolamine, PHEN) were studied in weanling rats pair-fed isocaloric diets containing either normal (NP, 23%) or low (LP, 6%) protein. Mean arterial pressure (MAP) rose less with NE and fell more with PHEN in LP than in NP. Plasma NE and epinephrine (E; 46 ± 5 and 51 ± 4 ng/ml) were higher in LP than in NP (26 ± 3 and 39 ± 3 ng/ml). These could not be attributed to changes in red cell mass nor the volumes of plasma, extracellular, or interstitial fluid in LP versus NP. Plasma angiotensin II (Ang II), renin (PRA), and aldosterone (PA) were lower in LP than in NP. An increased number without changes in affinity of glomerular Ang II receptors was found in LP compared to NP, while α 1 - and α 2 -adrenergic receptors were down-regulated in LP as compared to NP without changes in affinity for the α 1 receptor but with an increase in renal α 2 receptor affinity. LP (vs. NP) decreased GFR and RPF, and increased renal vascular resistance (RVR). NE decreased RPF equally in NP versus LP but raised RVR approximately twofold in NP versus LP. PHEN decreased RPF and increased RVR less in LP than in NP. Moreover, PHEN increased renal renin content approximately sevenfold over the basal NP values. Exogenous Ang II increased RVR and lowered RPF more in LP than in NP. Enalapril abolished all the hemodynamic changes of LP and restored the systemic response to NE. These findings are evidence that short periods of protein deprivation lead to systemic and local (intrarenal) alterations in adrenergic state and the renin-angiotensin system, and that these two are principally responsible for the adaptive hemodynamic changes observed. Dietary protein plays a significant role in the hormonal regulation of intrarenal hemodynamics.

Regulation of renin-angiotensin system in unilateral ureteral obstruction. The effect of 24-hour unilateral ureteral obstruction (UUO) on the expression and regulation of the renin-angiotensin system (RAS) in rats and of pretreatment with lisinopril (5 mg/kg/day) or the AT 1 -R inhibitor, losartan, (10 mg/kg/day) on renal hemodynamics was evaluated. Both drugs improved the post-obstructed kidney (POK) renal hemodynamics, lowered MAP, and normalized eicosanoid excretion by the POK. Cortex and medulla POK:CK ratio of relative density R mRNA was ˜3.5 for both. Sham, POK, and CK showed renin immunoreactivity and R mRNA exclusively in juxtaglomerular position. In addition, in POK renin was expressed in mesangial cells, along greater lengths of afferent arterioles and in dilated distal tubules and loops of Henle. In situ hybridization revealed that ˜20% more glomeruli in POK than CK overexpressed R mRNA. Blood vessels of POK consistently showed greater ACE and Ao mRNA expression than CK. Overexpression of the genes coding for members of the RAS is possibly responsible for local Ang II production which, in view of the response to CEI and AT 1 R inhibitors, is at least partly responsible for the severe hemodynamic changes in UUO.