Blockade of calcium channels and AT1 receptor prevents the hypertensive effect of calcilytic NPS 2143 in rats.
Calcilytics, antagonists of calcium receptor, decrease sensitivity of this receptor to plasma calcium concentration and increase parathyroid hormone (PTH) secretion. Moreover, it was recently indicated that calcilytic NPS 2143 induces hypertension in rats. This study tested whether the increase of mean arterial blood pressure (MAP) induced by NPS 2143 administration is mediated by calcium channel and angiotensin II type 1 (AT1) receptor activity. Wistar rats were anaesthesized with Thiopental i.p. and infused i.v. with saline supplemented with the anaesthetic. Blood pressure was monitored continuously in the carotid artery. Effects of NPS 2143 administered i.v. as bolus on MAP in the presence and absence of felodypine and losartan were investigated. Both, felodipine and losartan pretreatment provoked a persistent DMAP decrease by 18+/-3 and 14+/-3 mmHg, respectively. Infusion of NPS 2143 at 1 mg/kg b.w. confirmed hypertensive activity of calcilytic and increased blood pressure for 21+/-4 mmHg. In contrast, administration of NPS 2143 in felodipine as well as in losartan pretreated rats did not change DMAP as compared to felodipine/control and losartan/control groups, respectively. Our study indicated that both the blockade of calcium channels and the AT1 receptor activity prevented the hypertensive effect of calcilytic NPS 2143. This finding might be particularly important in understanding the mechanisms that mediated blood pressure changes related to the activity of calcium receptor.
Rybczynska
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Department of Pathophysiology, Medical University of Gdansk, Gdansk, Poland. aryb@gumed.edu.pl
Jurska-Jasko
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Boblewski
K
K
Lehmann
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A
Orlewska
C
C
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D015736:Felodipine / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors
D047228:Angiotensin II Type 1 Receptor Blockers; D002121:Calcium Channel Blockers; D015220:Calcium Channels; C436740:N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine; D009281:Naphthalenes; D044140:Receptor, Angiotensin, Type 1; D044169:Receptors, Calcium-Sensing; D019808:Losartan; D015736:Felodipine