Upregulation Of Renal Angiotensinogen In Male But Not Female Sd Rats During Angiotensin-Ii Induced Hypertension

Low doses of Angiotensin (Ang) II gradually increase blood pressure (BP), enhance salt sensitivity and renal accumulation of angiotensinogen (AGT). The goal of this study was to evaluate BP, renal damage and renal accumulation of AGT in response to Ang II in male and female SD rats (n=9). Rats received saline or Ang II (150 ng/kg/min SC) for 3 weeks, and were fed a 0.4% NaCl diet for 1 week and then a 4% NaCl diet. BP was recorded by telemetry. Renal damage was assessed by proteinuria and abuminuria and renal AGT by Western blot. Males given Ang II exhibited higher BP than females during high salt intake (140.1±1.7 vs 122.8±1.7 mmHg, p<0.05), and males excreted significantly more protein than females on either diet. Proteinuria in females did not change with Ang II or high NaCl despite 25 mmHg increase in BP. Albuminuria was also higher in males than females (21.1±4.9 vs. 1.8±1.2 mg/24h; p=0.01). In addition, males given Ang II had higher renal cortical expression of AGT than females (0.47±0.02 vs 0.28±0.02 AU, p<0.01) and control animals. Conclusion: Females are protected against renal damage during Ang II infusion and salt overload. Accumulation of AGT suggests activation of renal renin-angiotensin system as a possible mechanism for enhanced susceptibility to renal injury in males. Understanding the sex differences in susceptibility to renal injury may impact future therapeutic approaches in humans.