This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakamura, Y. Articles by Frohlich, E. D. Search for Related Content PubMed PubMed Citation Articles by Nakamura, Y. Articles by Frohlich, E. D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB AMLODIPINE BESYLATE Medline Plus Health Information Blood Pressure Medicines High Blood Pressure Related Collections Animal models of human disease Hypertension - basic studies Receptor pharmacology

(Hypertension. 1999;34:273-278.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Differential Effects of T- and L-Type Calcium Antagonists on Glomerular Dynamics in Spontaneously Hypertensive Rats

Yasuyuki Nakamura; Hidehiko Ono; Edward D. Frohlich

From the Hypertension Research Laboratories, Alton Ochsner Medical Foundation, New Orleans, La.

Correspondence to Edward D. Frohlich, MD, Vice President for Academic Affairs, Alton Ochsner Medical Foundation, 1516 Jefferson Hwy, New Orleans, LA 70121.

Abstract—To determine whether there is a difference in the effects of T- and L-type calcium antagonists on systemic, renal, and glomerular hemodynamics, the pathological changes of N^G-nitro-L-arginine methyl ester (L-NAME)–exacerbated nephrosclerosis and clinical alterations were investigated in spontaneously hypertensive rats (SHR). Seven groups of 17-week-old male SHRs were studied: Group 1, control; Group 2, mibefradil, 50 mg · kg^-1 · d^-1; Group 3, L-NAME in drinking water, 50 mg/L; Group 4, L-NAME (50 mg/L) plus mibefradil (50 mg · kg^-1 · d^-1); Group 5, L-NAME (50 mg/L) plus amlodipine (10 mg · kg^-1 · d^-1); Group 6 and 7, L-NAME (50 mg/L) for 3 weeks followed by mibefradil (50 mg · kg^-1 · d^-1) or amlodipine (10 mg · kg^-1 · d^-1), respectively, for the subsequent 3 weeks. Both the T- and L-channel calcium antagonists similarly reduced mean arterial pressure and total peripheral resistance index. These changes were associated with significant decreases in afferent and efferent glomerular arteriolar resistances and the ultrafiltration coefficient (P<0.01). Furthermore, the histopathological glomerular and arterial injury scores and urinary protein excretion were also significantly improved (P<0.01), and left ventricular and aortic masses were significantly diminished in all treated groups. Both drugs, mibefradil and amlodipine, had effects of increasing the single-nephron glomerular filtration ratio (SNGFR), and single-nephron plasma flow (SNPF), and of reducing glomerular afferent arteriolar resistance and urinary protein excretion. Thus, the T-type (mibefradil) and L-type (amlodipine) calcium antagonists each prevented and reversed the pathophysiological alterations of L-NAME–exacerbated hypertensive nephrosclerosis in SHR. The T-type calcium antagonist (mibefradil) seemed to have been more effective than the L-type amlodipine antagonist and it produced a greater reduction in afferent arteriolar resistance while preserving SNGFR.

Key Words: L-type receptor calcium antagonist • mibefradil • amlodipine • systemic hemodynamics • L-NAME • glomerular arteriolar injury • proteinuria • T-type receptor calcium antagonist • renal hemodynamics • glomerular dynamics • arteriolar injury

This article has been cited by other articles:

				K. Hayashi, S. Wakino, N. Sugano, Y. Ozawa, K. Homma, and T. Saruta Ca2+ Channel Subtypes and Pharmacology in the Kidney Circ. Res., February 16, 2007; 100(3): 342 - 353. [Abstract] [Full Text] [PDF]

				M.-G. Feng and L. G. Navar Nitric oxide synthase inhibition activates L- and T-type Ca2+ channels in afferent and efferent arterioles Am J Physiol Renal Physiol, April 1, 2006; 290(4): F873 - F879. [Abstract] [Full Text] [PDF]

				M.-G. Feng, M. Li, and L. G. Navar T-type calcium channels in the regulation of afferent and efferent arterioles in rats Am J Physiol Renal Physiol, February 1, 2004; 286(2): F331 - F337. [Abstract] [Full Text] [PDF]

				X. Zhou and E. D. Frohlich Ageing, hypertension and the kidney: new data on an old problem Nephrol. Dial. Transplant., August 1, 2003; 18(8): 1442 - 1445. [Full Text] [PDF]

				X. Zhou and E. D. Frohlich Ageing, hypertension and the kidney: new data on an old problem Nephrol. Dial. Transplant., August 1, 2003; 18(88): 1442 - 1445. [Full Text]

				M. Salomonsson, F. Gustafsson, D. Andreasen, B. L. Jensen, and N.-H. Holstein-Rathlou Local electric stimulation causes conducted calcium response in rat interlobular arteries Am J Physiol Renal Physiol, September 1, 2002; 283(3): F473 - F480. [Abstract] [Full Text] [PDF]

				H. Ono, Y. Ono, A. Takanohashi, H. Matsuoka, and E. D. Frohlich Apoptosis and Glomerular Injury After Prolonged Nitric Oxide Synthase Inhibition in Spontaneously Hypertensive Rats Hypertension, December 1, 2001; 38(6): 1300 - 1306. [Abstract] [Full Text] [PDF]

				E. D. Frohlich Local Hemodynamic Changes in Hypertension: Insights for Therapeutic Preservation of Target Organs Hypertension, December 1, 2001; 38(6): 1388 - 1394. [Abstract] [Full Text] [PDF]

				L. L. Cribbs Vascular Smooth Muscle Calcium Channels: Could "T" Be a Target? Circ. Res., September 28, 2001; 89(7): 560 - 562. [Full Text] [PDF]

				Y. Ozawa, K. Hayashi, T. Nagahama, K. Fujiwara, and T. Saruta Effect of T-Type Selective Calcium Antagonist on Renal Microcirculation: Studies in the Isolated Perfused Hydronephrotic Kidney Hypertension, September 1, 2001; 38(3): 343 - 347. [Abstract] [Full Text] [PDF]

				Y. Nakamura, H. Ono, X. Zhou, and E. D. Frohlich Angiotensin Type 1 Receptor Antagonism and ACE Inhibition Produce Similar Renoprotection in N{{omega}}-Nitro-L>-Arginine Methyl Ester/Spontaneously Hypertensive Rats Hypertension, May 1, 2001; 37(5): 1262 - 1267. [Abstract] [Full Text] [PDF]

				K. A. Griffin, M. Picken, G. L. Bakris, and A. K. Bidani Comparative Effects of Selective T- and L-Type Calcium Channel Blockers in the Remnant Kidney Model Hypertension, May 1, 2001; 37(5): 1268 - 1272. [Abstract] [Full Text] [PDF]

				E. D Frohlich Review: Promise of prevention and reversal of target organ involvement in hypertension Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S4 - S9. [PDF]

				D. Casellas, A. Herizi, A. Artuso, A. Mimran, and B. Jover Candesartan prevents L-NAME-induced cardio-renal injury in spontaneously hypertensive rats beyond hypotensive effects Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S84 - S90. [Abstract] [PDF]

				M. d. Gasparo, P. Hess, B. Nuesslein-Hildesheim, P. Bruneval, and J.-P. Clozel Combination of non-hypotensive doses of valsartan and enalapril improves survival of spontaneously hypertensive rats with endothelial dysfunction Journal of Renin-Angiotensin-Aldosterone System, June 1, 2000; 1(2): 151 - 158. [Abstract] [PDF]