A study of the action of amlodipine on adrenergically regulated sodium handling by the kidney in normotensive and hypertensive rats.
1. An investigation was undertaken to examine the effect of calcium channel blockade, induced by amlodipine, on the ability of the renal sympathetic nerves to cause an antidiuresis and anti-natriuresis in normotensive Sprague Dawley and spontaneously hypertensive rats anaesthetized with pentobarbitone. 2. Low frequency renal nerve stimulation in normotensive rats, which did not change renal blood flow, caused a 15% reduction in glomerular filtration rate and was associated with falls in urine flow of 37%, absolute sodium excretion of 47%, and fractional sodium excretion of 38%. The magnitude of these renal excretory changes was unaffected by prior administration of amlodipine at either 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1. Amlodipine given in the higher dose, decreased basal levels of blood pressure and increased basal urine flow and sodium excretion. 3. In spontaneously hypertensive rats, renal nerve stimulation minimally affected renal haemodynamics but decreased urine flow, absolute and fractional sodium excretion by 29%, 31% and 24%, respectively. 4. Similar renal nerve stimulation in spontaneously hypertensive rats given amlodipine at 200 micrograms kg-1 plus 50 micrograms kg-1 h-1 or 400 micrograms kg-1 plus 100 micrograms kg-1 h-1 caused minimal changes in renal haemodynamics and in the excretion of water and sodium. The higher dose of drug resulted in decreased blood pressure and increased basal rates of urine flow and sodium excretion. 5. These data show that in spontaneously hypertensive rats but not normotensive rats, calcium channel blockade inhibited the ability of the renal nerves to stimulate the reabsorptive processes for sodium at the renal tubule. This indicated that in spontaneous hypertension the post-receptor mechanisms had changed and become more dependent on the inward movement of calcium.
Johns
E J
EJ
Department of Physiology, Medical School, Birmingham.
D017311:Amlodipine; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000294:innervation / Q000378:metabolism*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology*; D014867:Water / Q000378:metabolism
D002121:Calcium Channel Blockers; D014867:Water; D017311:Amlodipine; D012964:Sodium; D009543:Nifedipine