Beneficial effects of calcium channel blockade on acute glomerular hemodynamic changes induced by cyclosporine

• Published in: American journal of kidney diseases Vol. 33; no. 2; pp. 267 - 275
• Main Authors: Fassi, Annamaria, Sangalli, Fabio, Colombi, Francesca, Perico, Norberto, Remuzzi, Giuseppe, Remuzzi, Andrea
• Format: Journal Article
• Language: English
• Published: Orlando, FL Elsevier Inc 01-02-1999; Elsevier
• Subjects: Acute Disease; Animals; Antihypertensive agents; Antihypertensive Agents - pharmacology; Biological and medical sciences; Calcium Channel Blockers - pharmacology; Cardiovascular system; Cyclosporine; Cyclosporine - adverse effects; Dihydropyridines - pharmacology; Drug toxicity and drugs side effects treatment; glomerular capillary pressure; glomerular filtration rate; Glomerular Filtration Rate - drug effects; glomerular hemodynamics; Hemodynamics - drug effects; Immunosuppressive Agents - adverse effects; Kidney Glomerulus - drug effects; Male; Medical sciences; MWF rat; Pharmacology. Drug treatments; Rats; Rats, Wistar; Time Factors; Toxicity: urogenital system; ultrafiltration coefficient; ultrafiltration coefficient; glomerular hemodynamics; MWF rat; Cyclosporine; glomerular filtration rate; glomerular capillary pressure; Kidney disease; Human; Glomerulonephritis; Coefficient; Urinary system disease; Glomerular filtration; Toxicity; Treatment efficiency; Calcium antagonist; Kidney; Ultrafiltration; Blood capillary; Ciclosporin; Blood pressure; Hemodynamics
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1016/S0272-6386(99)70299-4

Experimental and human studies have documented that cyclosporine (CsA) acutely reduces glomerular filtration rate (GFR). It has been reported that this effect can be partially prevented by calcium (Ca) channel blockade; however, the mechanisms by which this combination exerts its beneficial effects are unknown. We evaluated glomerular ultrafiltration determinants during acute CsA administration in the rat. First, we determined that maximal whole-kidney functional changes occur between 120 and 150 minutes after CsA administration and confirmed that pretreatment of MWF rats with the Ca channel blocker lacidipine effectively prevents a reduction in GFR. Micropuncture measurements in CsA-treated animals showed that a reduction in GFR (0.49 ± 0.24 v 0.88 ± 0.26 mL/min; P < 0.05; CsA-treated v untreated rats) is associated with a significant increase in glomerular capillary pressure (Pgc ; 63.1 ± 2.1 v 52.8 ± 2.8 mm Hg; P < 0.01) and efferent arteriolar resistance, whereas single-nephron (SN) GFR and ultrafiltration coefficient (Kf ) are both importantly reduced (34.0 ± 11.7 v 68.9 ± 23.8 nL/min; P < 0.05 and 1.04 ± 0.33 v 4.40 ± 2.36 nL/min/mm Hg; P < 0.01, respectively). Lacidipine partially prevented SNGFR (43.1 ± 14.3 nL/min) and Kf decline (2.08 ± 1.10 nL/min/mm Hg) despite the presence of elevated Pgc . This study further documents that Ca channel blockade has favorable effects on CsA-induced acute renal dysfunction. The mechanism of protection includes the prevention of glomerular hemodynamic changes induced by CsA, mainly GFR decline and reduction in glomerular Kf .