Effect of felodipine on blood pressure, body sodium, plasma renin activity and plasma aldosterone in hypertensive and normotensive rats.
1. To explore its effect on blood pressure (BP) in relation to body sodium (Na), felodipine was given to New Zealand genetically hypertensive (GH) and normotensive (N) rats and to Japanese SHR and WKY rats, prepared for repeated measurements of body sodium (Na) by a whole body counting technique (22Na) using an Na-free pelleted diet and 22Na-NaCl fluid as the sole source of Na, with water also available. The drug was added to the food before pelleting pellets, 0.5 mg/g food. 2. Felodipine reduced BP in each strain; this effect was as great on normal Na intake as when on a zero Na intake. Felodipine caused an increase in plasma renin activity in each strain but the increase reached significant levels only in GH, SHR and WKY. Plasma aldosterone was decreased by treatment in GH and N and increased in SHR and WKY. 3. In rats on a zero Na intake (water sole drinking fluid), felodipine caused no fall in body Na (i.e. no natriuretic effect was detectable) except in WKY. When saline was freely available, felodipine tended to stimulate saline intake and was associated with an increase in body Na in all strains except SHR; body Na was high in SHR even in the absence of felodipine and did not increase further with felodipine treatment. Felodipine slightly speeded up the excretion of an Na load in rats on an ample NaCl intake (choice of 0.5% 22Na-NaCl and water) but this may have been due, in part, to the treated rats having taken, by choice, a greater intake of saline in the pre-load period. 4. In this study, felodipine reduced BP and stimulated PRA and salt appetite. Its effects on Na handling varied to some extent between the strains; there was no consistent natriuretic effect, but rather some evidence of Na retention.
Ledingham
J M
JM
Department of Pharmacology and Wellcome Medical Research Institute, University of Otago Medical School, Dunedin, New Zealand.
Hamada
M
M
Simpson
F O
FO
D000450:Aldosterone / Q000097:blood*; D000803:Angiotensin I / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015736:Felodipine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood*; D012964:Sodium / Q000378:metabolism*; D012979:Sodium Radioisotopes
D000959:Antihypertensive Agents; D012979:Sodium Radioisotopes; D000450:Aldosterone; D000803:Angiotensin I; D012964:Sodium; D012083:Renin; D015736:Felodipine