Kinins modulate the sodium-dependent autoregulation of renal medullary blood flow

In the recent past it has become clear that the kallikrein-kinin system is closely intertwined with long-term blood pressure regulation. It was shown that a kinin B2 receptor blockade leads to a sodium-dependent rise in blood pressure. The underlying mechanisms of this phenomenon, however, remain unclear. The osmotic gradient of the renal medulla is a prerequisite for the preservation of volume and sodium by the kidney. We thus hypothesized, that a kinin dependent modulation of medullary blood flow accounts for the influence of sodium on blood pressure.

In 39 urethane anaesthetized rats pressure dependent regulation of whole kidney blood flow and cortical and medullary blood flow were estimated via laser-Doppler flux by a stepwise reduction of renal perfusion pressure to 30 mm Hg.

In controls (n = 15), a reduction in renal perfusion pressure to 30 mm Hg lead to a concomitant reduction in whole kidney blood flow (25 +/- 3% of baseline) and cortical laser-Doppler flux (36 +/- 5% of baseline). In contrast, medullary laser-Doppler flux decreased only to 79 +/- 8% of the baseline level. Providing a 2% sodium chloride solution as drinking water over 5 days (n = 12), resulted in a significantly lower capability to autoregulate medullary flow (50 +/- 6% of baseline, P < 0.05). Acute subcutaneous administration of Hoe 140, a bradykinin B2 receptor antagonist (300 micrograms/kg bwt), restored autoregulation of medullary flow to almost normal levels (93 +/- 12% of baseline, P < 0.01 versus high sodium diet alone, n = 12).

Our results indicate that B2 receptor blockade restores the attenuated autoregulation of medullary Doppler flux during sodium enriched diet. This, suggests that the kinin dependent impact of sodium on blood pressure regulation is mediated by modulations of medullary blood flow autoregulation.