The effect of a calcium antagonist and ATP on blood pressure in a rat model of pheochromocytoma

1993 Fiscal Year Final Research Report Summary

• Project/Area Number: 03404049
• Research Category: Grant-in-Aid for General Scientific Research (A)
• Allocation Type: Single-year Grants
• Research Field: Urology
• Research Institution: University of Tokyo
• Principal Investigator: HOMMA Yukio Department of Neurosurgery, Tokyo University Hospital, Assistant Professor, 医学部(病), 講師 (40165626)
• Co-Investigator(Kenkyū-buntansha): HIGASHIHARA Eiji Department of Neurosurgery, Tokyo University Hospital, Associate Professor, 医学部(病), 助教授 (00092312)
• Project Period (FY): 1991 – 1993
• Keywords: rat / pheochromocytoma / PC-12 / catecholamine / prazosion / nifedipine

Research Abstract

First, we attempted to produce a rat model for pheochromocytoma. Ten- to twelve-week-old New England Deaconness Hospital (NEDH) rats were inoculated, subcutaneously in the interscapular region, with 0.5*10^6 pheochromocytoma cells (PC-12). After inoculation, tumors first became palpable after 3-4 weeks. Systolic blood pressue and heart rate elevations were first noted 5-6 weeks after inoculation. Urinary excretion of catecholamines was increased 4 weeks after inoculation. In paticular, urinary excretions of norepinephrine and dopamine were significantly higher in pheochromocytoma-bearing animals compared to controls.
Then, the hypotensive effect, and the effect of inhibiting catacholamine release, of the calcium antagonist nifedipine, were studied in this rat model for pheochromocytoma, in comparision with the alpha adreneregic receptor antagonist prazosin. At the time tumors became palpable, tumor-bearing animals were assigned to one of various treatment groups : pheochromocytoma alone (untreated), prazosin hydrochloride (1mg/kg/day), and nifedipine (3mg/kg/day). Eight weeks following inoculation, the untreated rats were markedly hypertensive compared to controls. Nifidipine lowered blood pressure to the same degree that prazosin did. Urinary excretion of catecholamines was similarly increased in the pheochromocytoma rats administered the various drug regimens. Catecholamine contents in the tumors were not significantly different between them.
The results suggests that both nifidipine and prazosin are effective in lowering blood pressure in pheochromocytoma rats, but they have no ability to inhibit catecholamine release from pheochromocytoma cells.