| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1987: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1986: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
The present study was performed to clarify the antihypertensive effects of calcium entry blockers using anesthetized dogs and pithed rats.
1. Intrarenal infusion of nifedipine and CD-349, calcium entry blockers, produced marked increase in urine flow rate and in urinary sodium and potassium excretion rates of the infused kidney without changes in heart rate, glomerular filtration rate and filtration fraction. Urinary osmolarity was decreased by the drugs. The blood flow to the infused kidney was increased. These results suggest that nifedipine and CD-349 have striking effects on the reabsorption of sodium and water by the renal tubule (Reference 1).
2. Intrarenal infusion of nifedipine and CD-349 dose-dependently suppressed the renal vasoconstriction induced by intrarenal injections of angiotensin II (AII) or norepinephrine but not that by renal nerve stimulation. Furthermore, a greater renal vasodilation induced by intrarenal bolus injections of nifedipine but not acetylcholine was obse
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rved during the reduction of the perfusion pressure of the contralateral kidney, which resulted in an increase in plasma renin activity and plasma AII concentration (Reference 2).
3. In pithed rats, nifedipine inhibited the vasoconstrictor responses to alpha-2-adrenoceptor agonist B-HT 920, and AII but not to the alpha-1-adrenoceptor agonist methoxamine, and vasopressin. CD-349 reduced the pressor responses to all the above agonists. After pretreatment of calcium channel promotor Bay K 8644, the inhibition of CD-349 observed for AII, B-HT 920 and vasopressin was antagonized. These results suggest that AII-, alpha-2-adrenoceptor-mediated vasoconstrictions are sensitive to calcium entry blockade with calcium antagonists, but the vasoconstriction induced by the alpha-1-adrenoceptor-mediated agonist is not primarily dependent upon an influx of calcium. And it is possible that transcellular calcium influx may be common pathway in the vasoconstriction elicited by alpha-2-agonist B-HT 920 and AII. Less
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