Document Detail


The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital-anaesthetized pigs with or without beta-adrenoceptor blockade.
MedLine Citation:
PMID:  2871886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of the 1,4-dihydropyridine derivative nisoldipine, infused intravenously (i.v.) at 3 different rates (0.25, 0.5 and 1.0 microgram kg-1 min-1), were studied in anaesthetized pigs on cardiovascular performance with or without beta-adrenoceptor blockade produced by propranolol. Nisoldipine caused dose-dependent decreases in arterial blood pressure (30%), systemic vascular resistance (30%) and left ventricular filling pressure (15%), but raised heart rate (25%) and LV dP/dt max (20%). Cardiac output was not significantly affected. Transmural myocardial blood flow and vascular conductances increased dose-dependently after nisoldipine. The elevation in blood flow to the left ventricle favoured epicardial layers. Endocardial blood flow showed small increases as the changes in conductance of the endocardial layer more than compensated for the loss in perfusion pressure. The endo-epi blood flow ratio decreased from 1.16 +/- 0.05 to 0.70 +/- 0.01. Myocardial O2-consumption was unaltered as the decrease in arterial-coronary venous O2-content difference (30%) was balanced by the increase in transmural blood flow. Nisoldipine increased blood flow to skeletal muscle (500%), stomach (50%) and adrenals (25%), but decreased that to the liver (50%), spleen (25%) and kidneys (25%). No changes were noticed in the small intestine, skin and brain. In spite of differential effects on blood flow, vascular conductance in all organs and tissues, with the exception of the liver, increased. After beta-adrenoceptor blockade the responses of mean arterial blood pressure, cardiac output and systemic vascular resistance to nisoldipine remained virtually unchanged, but the elevations in heart rate and LV dP/dt max were abolished, as was the decrease in left ventricular filling pressure. A higher dose of nisoldipine was required after beta-adrenoceptor blockade to elicit significant vasodilatation in the epi- and endocardial layers. However, the reduction in endo-epi blood flow ratio by nisoldipine was not affected by propranolol. Myocardial O2-consumption tended to decrease as the diminution in the arterial-coronary venous O2-content difference (30%) slightly exceeded the increase of left ventricular blood flow (30%). Except for the brain and liver, effects of nisoldipine on regional vascular conductances were attenuated after beta-adrenoceptor blockade.
Authors:
D J Duncker; J M Hartog; P G Hugenholtz; P R Saxena; P D Verdouw
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of pharmacology     Volume:  88     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1986 May 
Date Detail:
Created Date:  1986-07-18     Completed Date:  1986-07-18     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  9-18     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology*
Anesthesia
Animals
Calcium Channel Blockers / pharmacology*
Cardiac Output / drug effects
Coronary Circulation / drug effects
Hemodynamics / drug effects*
Myocardium / metabolism
Nifedipine / analogs & derivatives*,  pharmacology
Nisoldipine
Oxygen Consumption / drug effects
Pentobarbital
Regional Blood Flow / drug effects*
Swine
Vascular Resistance / drug effects
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Calcium Channel Blockers; 21829-25-4/Nifedipine; 63675-72-9/Nisoldipine; 76-74-4/Pentobarbital
Comments/Corrections

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