Angiotensin II inhibition increases diuresis during acute sympathetic activation in intact and denervated kidneys in rats with chronic myocardial infarction

Heart Vessels. 2022 Sep;37(9):1636-1646. doi: 10.1007/s00380-022-02110-2. Epub 2022 Jun 11.

Abstract

We examined urine excretion during primary acute sympathetic activation (PASA) in Wistar-Kyoto rats with myocardial infarction (MI). The rats underwent unilateral renal denervation (RDN) 7 weeks after coronary artery ligation. 4-10 days later, an acute experiment was performed under anesthetized conditions (n = 8 rats). Isolated carotid sinus pressure was changed stepwise from 60 to 180 mmHg, and the relationship between the arterial pressure (AP) and the normalized urine flow (nUF, urine flow normalized by the body weight) was examined. After obtaining the control data, an angiotensin II type 1 receptor blocker telmisartan (2.5 mg/kg) was intravenously administered. The effects of RDN, telmisartan, and heart weight (biventricular weight) on the relationship between AP and nUF were examined using multiple regression analyses. Regarding the slope of nUF versus AP (nUFslope), the constant term of the regression was positive (0.315 ± 0.069 μL·min-1·kg-1·mmHg-1), indicating that nUF increased with AP. The heart weight had a negative effect on nUFslope (P < 0.05), suggesting that the severity of MI was associated with the impairment of urine excretion. Telmisartan increased nUFslope by 0.358 ± 0.080 μL·min-1·kg-1·mmHg-1 (P < 0.001), whereas RDN had no significant effect on this parameter. The results indicate that unilateral RDN was unable to abolish the effect of the renin-angiotensin system on urine excretion during PASA. Circulating or locally produced angiotensin II, rather than ongoing renal sympathetic nerve activity, played a dominant role in the impairment of urine excretion during PASA in rats with chronic MI.

Keywords: Angiotensin II; Arterial pressure; Myocardial infarction; Open-loop analysis; Pressure diuresis.

MeSH terms

  • Angiotensin II* / pharmacology
  • Animals
  • Blood Pressure
  • Diuresis
  • Kidney
  • Myocardial Infarction*
  • Rats
  • Rats, Inbred WKY
  • Sympathetic Nervous System
  • Telmisartan / pharmacology

Substances

  • Angiotensin II
  • Telmisartan