Effect of felodipine treatment and withdrawal on blood pressure and cardiovascular structure in New Zealand genetically hypertensive rats.
1. Four groups of New Zealand genetically hypertensive (GH) rats were treated with felodipine as follows: (A) from ages 4-12 weeks; (B) 4-20 weeks; (C) 4-12 weeks then withdrawn from felodipine till age 20 weeks; and (D) 12-20 weeks. 2. Effects on blood pressure (BP), left ventricular (LV) weight and the structure of myograph-mounted mesenteric resistance arteries (MRA) were measured. 3. BP was about 170 mmHg in 4 week old GH rats and did not change substantially from this value in groups A and B but rose to over 230 mmHg in untreated controls. In rats of group D, started on felodipine at 12 weeks, BP fell rapidly and was 173 mmHg at 20 weeks. On withdrawal of felodipine at 12 weeks (group C) BP rose rapidly and exceeded control levels at 20 weeks. 4. LV mass was significantly lower (P < 0.001) in all groups (A, B and D) killed while on felodipine but rose to control levels in the rats taken off felodipine. 5. In the four treated groups there were no significant changes in MRA structure (lumen diameter, medial thickness, media/lumen ratio and volume of medial tissue) as measured on the myograph. 6. Felodipine induces substantial falls in BP in GH rats which are sufficient to prevent cardiac hypertrophy but do not alter MRA structure. Resistance artery structure in GH rats does not seem to relate to the level of hypertension, and may therefore not have a necessary role in the pathogenesis of this hypertensive strain.
Ledingham
J M
JM
Department of Pharmacology, University of Otago Medical School, Dunedin, New Zealand.
Phelan
E L
EL
Cross
M A
MA
Laverty
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000473:pathology*; D015736:Felodipine / Q000009:adverse effects* / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D015736:Felodipine