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Differential effects of T- and L-type calcium antagonists on glomerular dynamics in spontaneously hypertensive rats.

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.
AuthorsY Nakamura, H Ono, E D Frohlich
JournalHypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 34 Issue 2 Pg. 273-8 (Aug 1999) ISSN: 0194-911X [Print] United States
PMID10454453 (Publication Type: Comparative Study, Journal Article)
Chemical References
  • Antihypertensive Agents
  • Benzimidazoles
  • Calcium Channel Blockers
  • Calcium Channels
  • Enzyme Inhibitors
  • Tetrahydronaphthalenes
  • Vasodilator Agents
  • Amlodipine
  • Uric Acid
  • Mibefradil
  • Creatinine
  • NG-Nitroarginine Methyl Ester
Topics
  • Amlodipine (pharmacology, therapeutic use)
  • Animals
  • Antihypertensive Agents (pharmacology, therapeutic use)
  • Benzimidazoles (pharmacology, therapeutic use)
  • Calcium Channel Blockers (pharmacology, therapeutic use)
  • Calcium Channels (drug effects)
  • Creatinine (blood)
  • Data Interpretation, Statistical
  • Enzyme Inhibitors (pharmacology)
  • Glomerular Filtration Rate
  • Heart (drug effects)
  • Hemodynamics (drug effects)
  • Hypertension (chemically induced, drug therapy)
  • Kidney (drug effects)
  • Kidney Glomerulus (drug effects)
  • Kidney Tubules (drug effects)
  • Male
  • Mibefradil
  • NG-Nitroarginine Methyl Ester (administration & dosage)
  • Nephrocalcinosis (drug therapy)
  • Organ Size
  • Rats
  • Rats, Inbred SHR
  • Tetrahydronaphthalenes (pharmacology, therapeutic use)
  • Uric Acid (blood)
  • Vasodilator Agents (pharmacology, therapeutic use)

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