Effects of diltiazem and allopurinol in postischemic microcirculatory changes in the rat kidney.
The influence of diltiazem and/or allopurinol on kidney microcirculation was studied in anaesthetized rats, which were subjected to 60 min unilateral renal ischemia followed by 60 min reflow. In histological sections capillary plasma flow patterns were determined based on the distribution of two different fluorochrome-labelled globulins administered i.v.. In the outer medulla (OM) of untreated postischemic kidneys labelling of the capillary network was greatly diminished. Tissue areas occupied by red blood cells increased 4-6 fold. During reperfusion massive penetration of red cells in the urine was demonstrated by the occurrence of hemoglobin in the urine. Maintenance of the rats on allopurinol-saturated drinking water for six days prior to the experiment (daily intake approximately 50 mg allopurinol/kg body wt) combined with the i.v. administration of diltiazem during the pre- and postischemic period (16 mg/kg body wt) resulted in an almost complete normalization of capillary plasma flow patterns in the OM. In this region tissue areas occupied by red blood cells were much lesser in extent than in the untreated controls. Furthermore, urine hemoglobin content after the combined drug regimen was largely decreased when compared to the untreated ischemic group. Effects of the treatment with either of the drugs alone were qualitatively similar, but significantly less pronounced. In conclusion, a synergistic effect of diltiazem and allopurinol in improving postischemic renal microcirculation is clearly evident, whereas no improvement in kidney function was demonstrable. This supports the hypothesis that disturbed microcirculation is not a prerequisite for the generation of the renal functional deterioration in the clamp-induced ischemia model in the rat.
Pethö-Schramm
A
A
Institut für Pharmakologie und Toxikologie, Universität Göttingen, Germany.
Mielke
W
W
Vetterlein
F
F
Schmidt
G
G
D000493:Allopurinol / Q000494:pharmacology*; D000818:Animals; D002196:Capillaries / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology*; D004347:Drug Interactions; D004903:Erythrocyte Aggregation / Q000187:drug effects; D005916:Globulins / Q000378:metabolism; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D015427:Reperfusion Injury / Q000097:blood / Q000503:physiopathology*; D013997:Time Factors
D005916:Globulins; D000493:Allopurinol; D004110:Diltiazem