Renal and cardiovascular effects of acute and chronic administration of felodipine to SHR.
Renal function and salt and water turnover were studied in SHR during acute and chronic administration of felodipine, which is an efficient antihypertensive vasodilating Ca2+ antagonist. In conscious SHR acute administration of felodipine in hypotensive doses increased renal sympathetic nerve activity but caused renal vasodilation, increases in GFR and a 2-3 fold increase in urinary flow rate and sodium excretion. The fraction of filtered sodium excreted (FENa) was approximately doubled. The diuretic and natriuretic effects of felodipine are therefore suggested to be due to a direct inhibitory action on the renal tubular cells, resulting in reduced sodium reabsorption. Nifedipine also induced diuresis and natriuresis in this system, while minoxidil reduced water and sodium excretion. Throughout 6 months of felodipine treatment, the mean arterial pressure (MAP), remained 25-20 per cent reduced. Felodipine in combination with metoprolol reduced MAP 25-30 per cent and also caused regression of left ventricular hypertrophy, while felodipine alone prevented its further progression. Also during chronic administration, felodipine induced diuresis but had no effect on plasma volume and on sodium or potassium excretion in SHR. It is concluded that in SHR felodipine induces diuresis; on acute treatment this is secondary to reduced tubular sodium reabsorption, although during chronic treatment the sodium loss is compensated for while the diuresis remains. Thus, the cardiovascular and renal effects of Ca2+ antagonists like felodipine differ substantially from those of other potent antihypertensive vasodilators e.g. minoxidil.
Nordlander
M
M
Di Bona
G F
GF
Ljung
B
B
Yao
T
T
Thorén
P
P
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000188:drug therapy; D015736:Felodipine; D005665:Furosemide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D009543:Nifedipine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects
D000959:Antihypertensive Agents; D008914:Minoxidil; D005665:Furosemide; D012964:Sodium; D009543:Nifedipine; D015736:Felodipine