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The effects of nisoldipine (Bay K 5552) on cardiovascular performance and regional blood flow in pentobarbital ‐ anaesthetized pigs with or without β‐adrenoceptor blockade
Author(s) -
Duncker D.J.,
Hartog J.M.,
Hugenholtz P.G.,
Saxena P.R.,
Verdouw P.D.
Publication year - 1986
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1986.tb09465.x
Subject(s) - nisoldipine , vascular resistance , medicine , blood flow , blood pressure , propranolol , cardiac output , cardiology , endocrinology , nifedipine , calcium
1 The effects of the 1,4‐dihydropyridine derivative nisoldipine, infused intravenously (i.v.) at 3 different rates (0.25, 0.5 and 1.0 μg kg −1 min −1 ), were studied in anaesthetized pigs on cardiovascular performance with or without β‐adrenoceptor blockade produced by propranolol. 2 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. 3 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 O 2 ‐consumption was unaltered as the decrease in arterial‐coronary venous O 2 ‐content difference (30%) was balanced by the increase in transmural blood flow. 4 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. 5 After β‐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. 6 A higher dose of nisoldipine was required after β‐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 O 2 ‐consumption tended to decrease as the diminution in the arterial‐coronary venous O 2 ‐content difference (30%) slightly exceeded the increase of left ventricular blood flow (30%). 7 Except for the brain and liver, effects of nisoldipine on regional vascular conductances were attenuated after β‐adrenoceptor blockade.