title: Resetting baroreceptors to a lower arterial pressure level by enalapril avoids baroreflex mediated activation of sympathetic nervous system by nifedipine.
abstract: Baroreceptor-unloading-mediated activation of sympathetic nervous system (SNS) by antihypertensive agents, such as dihydropyridine calcium channel blockers (CCB), has been considered to compromise the beneficial effects of the therapy and lead to unsatisfying clinical outcome. The present study was aimed at finding a novel way of using CCB without activating SNS. In anaesthetized Wistar rats, baroreceptor-unloading-mediated reflex activation of SNS, as indicated by tachycardia and increase of plasma catecholamines, was observed after mean arterial pressure (MAP) was decreased by 15 mmHg during 4-h administration of nifedipine, a CCB. However an angiotensin-converting enzyme inhibitor (ACEI), enalapril did not cause tachycardia or increase plasma catecholamine levels when it decreased MAP by 15 mmHg. After 100 min (supposedly baroreceptor resetting or adaptation to hypotension had occurred), enalapril infusion was gradually replaced by nifedipine infusion in 40 min. Nifedipine was infused for another 100 min, which kept the lowered MAP unchanged and did not activate SNS. In anaesthetized spontaneously hypertensive rats (SHR), baroreceptor-mediated reflex activation of SNS was observed after MAP was decreased by 25 mmHg during 4-h nifedipine administration. However enalapril did not cause tachycardia or increase plasma catecholamine levels when it decreased MAP by 25 mmHg. After 100 min, enalapril infusion was gradually replaced by nifedipine infusion in 40 min. Nifedipine was then infused for another 100 min, which kept the lowered MAP unchanged and did not activate SNS. The present study indicated that reflex activation of SNS caused by antihypertensive effect of CCB could be avoided if, prior to CCB administration, baroreceptors have been reset to a lower MAP by a drug that does not activate baroreceptor reflex.
authors: Cardiovascular Institute and Fu Wai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing. wzhang@mednet.swmed.edu
authors: W
authors: W
authors: Zhang
authors: Z
authors: Z
authors: Wang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D004347:Drug Interactions; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use*; D004837:Epinephrine / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use*; D009638:Norepinephrine / Q000097:blood; D011311:Pressoreceptors / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000378:metabolism; D013610:Tachycardia / Q000139:chemically induced; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004656:Enalapril; D009543:Nifedipine; D009638:Norepinephrine; D004837:Epinephrine