Acute and Reversible Inhibition of Tubuloglomerular Feedback Mediated Afferent Vasoconstriction by the Calcium-antagonist Verapamil

Unlabelled: In order to analyze the role of afferent vasomotor activity in mediating tubuloglomerular feedback response, we studied the effect of the intravenously applied Ca++ antagonist Verapamil on proximal stop flow pressure (SFP). In Wistar rats SFP was recorded continuously upstream of a solid paraffin block under either zero or 50 nl/min loop perfusion rate with artificial tubular fluid. The latter elicits maximal feedback response. Similar experiments were performed on heminephrectomized rats which are known to exhibit a highly sensitive feedback response.

Results: Verapamil given as a single dose (0.05-0.15 mg/kg b.w., i.v.) resulted in a transient decrease of mean arterial blood pressure of about 10 to 20 mmHg (1 to 3 min), SFP was unaltered during zero loop perfusion. Verapamil applied during a feedback stimulated SFP decrease (50 nl/min loop perfusion) caused restoration of normal SFP for 6 to 10 min indicating an acute and reversible interference of this drug with feedback regulation. Reversal of feedback response was complete in both groups of rats irrespective of the large difference in their feedback sensitivity. Thus: 1. The Ca++ antagonist is a complete inhibitor of feedback mediated SFP changes, 2. decreased SFP during high loop perfusion rate could be titrated back to normal by continuous infusion of Verapamil (dose 0.04 mg/kg-min), 3. Furthermore, feedback regulation of SFP could be prevented by infusion of the drug just prior to increasing loop perfusion rate.