Diminished responses to nifedipine imply severe end-organ damage in spontaneously hypertensive rats.
This study was designed to investigate the effect of end-organ damage (EOD), the initial blood pressure levels, and baroreflex sensitivity (BRS) on the blood pressure-lowering effect of nifedipine in spontaneously hypertensive rats (SHRs). Nifedipine was intravenously administered at a dose of 1 mg/kg. BP was continuously recorded in the conscious state before and after nifedipine administration. BRS was determined before drug administration. Two days after the blood pressure (BP) recording, rats were killed for organ-damage evaluation. Univariate correlation analysis showed that BP changes induced by nifedipine injection were negatively correlated with EOD score and aortic weight/length but positively correlated with left kidney weight/body weight and basal BP levels. Stepwise multiple linear regression analysis demonstrated that increase in overall end-organ damage was most significantly related to the decrease in hypotensive effect of nifedipine; increase in aortic hypertrophy was also related to a decreased fall in systolic and diastolic BP induced by nifedipine, whereas increase in initial BP levels was associated with increased hypotensive effect of nifedipine. In conclusion, the severity of overall EOD contributed more than basal BP levels to the diminished responses to nifedipine, and aortic hypertrophy was also involved in diminished drug responses.
Lu
Li-Hua
LH
Department of Pharmacology, Second Military Medical University, Shanghai 200433, China.
Xie
He-Hui
HH
Cai
Guo-Jun
GJ
Shen
Fu-Ming
FM
Su
Ding-Feng
DF
D000818:Animals; D001011:Aorta / Q000473:pathology*; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000473:pathology*; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012044:Regression Analysis
D002121:Calcium Channel Blockers; D009543:Nifedipine