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H U Gutsche

Publications and source records attributed to H U Gutsche.

27 records · Page 2Linked to original sources

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.

Animals↗

Tubuloglomerular feedback in rat kidneys of different renin contents.

Variations in flow rate through the loop of Henle in the range of 0--50 nl/min were induced using pressure controlled microperfusion. Simultaneously, with the aid of a second pressure-microperfusionsystem, the glomerular function of the same nephron was studied by continuous measurement of two parameters, early proximal flow rate (EPFR) and/or stop flow pressure (SFP). Elevation of loop perfusion above physiological values (40 nl/min) resulted in a drop of EPFR and SFP, whereas lowering perfusion rates had no effect. This feedback behaviour was studied in kidneys with different renin contents to test the role of the renin-angiotensin system in the mediation of the macula densa signal to the adjacent glomerular vessels. Renal renin content, measured after micropuncture experiments by incubation with substrate followed by radioimmunoassay of angiotensin I, was unaltered in control (Ia) and heminephrectomized rats (Ib), lowered in contralateral kidneys of 2 kidneys Goldblatt hypertensive rats (IIa), in DOCA- and salt-loaded rats (IIb), and in DOCA-, salt-loaded and heminephrectomized rats (IIc), and it was evaluated in clipped kidneys of Goldblatt hypertension rats (IIIa). Micropuncture evaluation of the tubuloglomerular feedback behaviour in these experimental groups revealed the following results: 1. a feedback response under all conditions independent of the widely varying renin contents (1000-fold), 2. an asymmetrical behaviour of the feedback response in all kidneys as demonstrated by suppression of EPFR and SFP at elevated loop flow rates, but no change of these parameters when loop flow was interrupted. 3. compared to controls the decrease of each GFR parameter between 0 and 40 nl/min loop perfusion was lower in DOCA- and salt-loaded rats (IIb, IIc). Additional heminephrectomy (IIc) had no further influence on the reduced feedback response in DOCA- and salt-loaded rats, whereas this maneuver reduced the renal renin content drastically. A somewhat higher response than in controls was found in heminephrectomized rats (IIb) and in clipped kidneys of Goldblatt hypertensive rats (IIIa). These different magnitudes of feedback responses do not correlate with the renal renin content. It has been concluded, therefore, that renal renin activity is not the sole determinant of the effectiveness of the tubuloglomerular feedback response.

Angiotensin II↗

A new method for intratubular blockade in micropuncture experiments.

Criteria for a reliable blockade of tubular flow are generally discussed and experimental evidence is presented that solid paraffin meets all the necessary criteria in rat kidney tubules when an immobile and tight sealing intratubular blockade is requested. A special microinjection apparatus for the application of paraffin is described. Furthermore, several alternative methods and materials have been tested and have been found to be inferior to solid paraffin.

Animals↗