Effects of calcium antagonist felodipine on renal sympathetic nerve activity in rats with congestive heart failure.
In order to assess the effects of dihydropyridine calcium antagonist on sympathetic nerve activity (SNA) in experimental chronic heart failure (CHF), felodipine was given to rats with CHF induced by coronary artery ligation. Anesthetized CHF (n = 7) and sham-operated (n = 9) rats were injected with a bolus dose of felodipine (20 microg/kg) and then infused with felodipine (30 microg/kg/h) for 3 hours. Control CHF rats (n = 8) were given vehicle in the same way. After felodipine treatment, mean blood pressure (MBP) rapidly decreased to 75-85 mmHg, and there was a reflex tachycardia and reflex activation of renal SNA. The heart rate (HR) had returned to baseline level after 3 hours of continuous felodipine infusion, and the SNA returned to baseline level after 2 hours of infusion. At the end of the experiment, renal SNA was 65.4 +/- 11.5% of the baseline level in CHF rats receiving felodipine (P < 0.05) and 94.1 +/- 22.8% in CHF rats receiving vehicle (P > 0.05), but there was no statistical difference between the two groups. Arterial baroreceptor sensitivity (assessed by phenylephrine infusion), which was impaired in CHF rats (-2.7 +/- 0.2 SNA%/mmHg in all CHF rats together vs. -3.6 +/- 0.4 in sham-operated rats, P < 0.5) did not differ significantly from that in sham-operated rats during felodipine infusion (-3.2 +/- 0.4 in felodipine-treated CHF rats vs. -3.7 +/- 0.6 in sham-operated rats) but deteriorated without felodipine treatment (-2.1 +/- 0.3 in CHF rats receiving vehicle, P < 0.05). The biphasic renal SNA response during felodipine infusion suggests that felodipine does not cause persistent sympathetic activation and relatively improves baroreceptor sensitivity in CHF rats.
Zhang
W
W
Department of Clinical Pharmacology, University of Gothenburg and Sahlgrenska Hospital, Göteborg, Sweden. weizha@ki.se
Sun
X
X
Zhao
X
X
Thorén
P
P
Hedner
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D015736:Felodipine / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000294:innervation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects*
D002121:Calcium Channel Blockers; D015736:Felodipine