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Abstract: PO2142

Different Renal and Cerebral Vascular Responses to Angiotensin II Infusions in Anesthetized Mice: Roles of Vasodilator Prostaglandins and Nitric Oxide

Session Information

Category: Hypertension and CVD

  • 1403 Hypertension and CVD: Mechanisms

Authors

  • Wilcox, Christopher S., Georgetown University Medical Center, Washington, District of Columbia, United States
  • Solis, Glenn, Georgetown University Medical Center, Washington, District of Columbia, United States
  • Mendonca, Margarida, Georgetown University Medical Center, Washington, District of Columbia, United States
  • Welch, William J., Georgetown University Medical Center, Washington, District of Columbia, United States
Background

Since the cerebral PO2 is much lower than the renal, the brain requires protection from vasoconstriction while the renal circulation must adapt to physiological demands often dictated by angiotensin II (Ang II). We tested the hypothesis that renal and cerebral blood flow (RBF and CBF) are differentially regulated by vasodilator prostaglandins (PGs) and nitric oxide (NO).

Methods

Mice (n = 6 – 8 per group) were anesthetized with a-chloralose/urethane and ventilated to a PCO2 of 33-38 mmHg. Mean arterial pressure (MAP) was recorded via an aortic cannula, RBF via a transit time blood flow meter encircling a renal artery and CBF via a blood flow meter encircling the common carotid artery with the external carotid artery ligated. Renal and cerebral vascular resistances (RVR and CVR) were recorded on line during infusion of vehicle or Ang II (40 p mol min-1 Kg-1 iv) vs vehicle. L-NAME (30 mg-1 Kg-1 h-1) and/or indomethacin (5 mg-1 Kg-1 h-1) or vehicle were infused iv over 50 mins to test the roles of NO and PGs in basal and Ang II-stimulated vascular resistances.

Results

In the basal state, L-NAME increased RVR (+79 ± 9%; P < 0.01) and CVR (+78 ± 8%; P < 0.01) similarly whereas vehicle was ineffective. Indomethacin alone did not modify RVR or CVR but enhanced the effects of L-NAME to raise RVR (+132 ± 15%; P < 0.05) and CVR (+134 ± 30%; P < 0.05) similarly. Thereafter, Ang II infusion increased MAP (+10 ± 2%; P < 0.05) and RVR (+33 ± 6%; P < 0.05) but did not change CVR (+2 ± 2%; NS). Neither L-NAME nor indomethacin alone modified the MAP, RVR or CVR responses to Ang II but after indomethacin given to mice infused with L-NAME, Ang II infusion caused a greater rise in MAP (+30 ± 3%; P < 0.05), and RVR (+190 ± 5%; P < 0.05) but CVR remained quite unresponsive (-7 ± 5%; NS).

Conclusion

Low basal RVR and CVR depend on PG-dependent NO generation. Whereas CVR is entirely protected from vasoconstriction with Ang II, the increase in RVR with Ang II is moderated by PG-dependent NO generation. Thus, PGs and NO exert distinct action in the renal and cerebral vasculature.