Influence of diltiazem on postischemic microcirculation and function in the rat kidney.
Renal microcirculation and function were studied in the unilateral clamp-induced ischemia/reperfusion model in anesthetized rats. After 60-min reperfusion fluorochromelabeled globulin was injected i.v. allowing histological determination of capillary plasma flow patterns (CPFP). In the 60-min ischemia protocol the untreated group revealed poor capillary labeling in the outer medulla (OM), whereas cortical perfusion patterns were only slightly altered. Pre- and postischemic treatment with diltiazem led to significant improvement of CPFP in the OM: 4.9% of tissue areas were lying more than 60 microns from the next perfused capillary vs 70.2% after untreated ischemia. Postischemic treatment with diltiazem proved much less effective. Inulin clearance (CIn) amounted to less than 2% of baseline values irrespective of the treatment regimen. However, in the 30-min ischemia protocol, displaying normal CPFP, preservation of CIn was evident and most effective after pre- and postischemic diltiazem treatment (53% vs 8% after untreated ischemia). Measurements of tubular function, however, did not reveal any significant improvement after diltiazem treatment. This observation and the fact that the drugs has a vasodilating effect lend support to the view that the preservation of glomerular filtration rate (GFR) is most likely mediated by vascular mechanisms. In conclusion, in this experimental model diltiazem significantly reduced postischemic disturbances of renal microcirculation occurring after prolonged periods of ischemia and was clearly efficient in maintaining GFR after shorter ischemic episodes; however, tubular function was not preserved. Our results, as well as those of other authors, strongly suggest that diltiazem causes the aforementioned effects mainly by actions at the vascular site.
Pethö
A
A
Zentrum Pharmakologie und Toxikologie, Georg-August-Universität Göttingen, Federal Republic of Germany.
Neumann
T
T
Vetterlein
F
F
Schmidt
G
G
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000503:physiopathology; D007677:Kidney Function Tests; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012079:Renal Circulation / Q000187:drug effects*; D015424:Reperfusion; D014665:Vasodilator Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D004110:Diltiazem