Eur J Clin Pharmacol (1990) 39:403-404
European,Iouma,of 1 ~ ( ~ : ~
@%QssaQ erle®9 @ Springer-Verlag 1990
Short communications
Effect of nifedipine monotherapy on platelet aggregation in patients with untreated essential hypertension* Z. Ogmia~owska 1, M. N a r t o w i c z - S t o n i e w s k a 3, J. M. S~omi/lski ~, a n d B. K r u p a - W o j c i e c h o w s k a 2 Department of Diagnostic Laboratory, 2 Second Clinic of Internal Diseases, Institute of Internal Medicine and 3 Department of Pathophysiology, Institute of Pathophysiology, Medical Academy, Gdafisk, Poland Received: April 19, 1989/Accepted in revised form: March 15, 1990
Summary. T h e effect of 6 weeks of nifedipine 30-60 mg/d on platelet aggregation and lipid p a r a m e t e r s has b e e n studied. A diminution in A D P - , adrenaline- and collagen-induced aggregation was observed. In the case of adrenaline- and collagen-stimulated aggregation the decrease was statistically significant. It was f o u n d that platelets which aggregated m a r k e d l y during the placebo t r e a t m e n t were most strongly inhibited by nifedipine. T h e changes in lipid p a r a m e t e r s were n o t significantly correlated with changes in aggregation.
Key words: nifedipine, hypertension; lipids, platelet aggregation
Calcium channel antagonists are amongst the m o s t comm o n l y used drugs in routine antihypertensive therapy. In spite of their wide applicability, the side-effects of these drugs are not fully known. T h e r e are few reports of the effects of nifedipine and b l o o d platelet function [Dale et al. 1983, N y r o p and Zweifler 1988, Walley et al. 1989]. T h e aim of the present study was to examine w h e t h e r and h o w p r o l o n g e d nifedipine t r e a t m e n t would affect platelet aggregation and lipid parameters, and what were the correlations b e t w e e n any p a r a m e t e r s affected.
30 min of supine rest. Every subject was examined by the same physician. Patients gave their informed consent to participation in the study. Nifedipine 30-60 mg/d was administered for 6 weeks after 2 weeks on placebo. The characteristics of the 15 hypertensive men under study are listed in Table 1.
Methods Blood was taken from the right antecubital vein by careful venepuncture without stasis and was collected in plastic tubes containing 1/10 volume sodium citrate (3.8%) for measurement of platelet aggregation. At the same time blood was collected for lipid tests according to the specific requirements. Platelet aggregation studies were performed using the turbidimetric method of Born [Born 1962]. Platelet rich plasma (PRP) was obtained by immediate centrifugation of the blood samples at 160 g for 10 rain at room temperature. The remaining blood was centrifuged at 3000 g for 20 min to obtain platelet poor plasma (PPP). The platelet count of the PRP was adjusted to 250-300 x 109.1- ~.An aggregometer Elvi 840 (ELVI S p.A. Milano, Italy) and Omniscribe ®recorder Logos 176 were used for this procedure. The PPP and PRP were used as 100% and 0% light transmission standards, respectively.
Table 1. Characteristics of the hypertensive patients (n = 15) Body weight (kg) Body mass index (kg.m-2)
Subjects Fifteen male patients aged 40-60 y (mean age 49.8 y) with mild to moderate untreated essential hypertension (WHO Group I -7, and Group II - 8 persons) were selected from outpatients attending the Department of Hypertension, Medical Academy of Gdafisk. The patients had no history or clinical evidence of vascular disease, diabetes mellitus, hepatic or haematological disorders. All subjects had normal urinalysis and renal function, as estimated by creatinine clearance. They were examined as outpatients and were at work. The patients were on a free diet with no restriction of sodium intake. None was addicted to alcohol or was taking any drugs. Smoking and food intake were not allowed for 12 h before sampling. The examinations were carried out between 08.30 and 09.00 h after * This rePort is a part of a project realized within the frames of the government programme of studies of the side-effects of hypotensive drugs given for i year.
Supine blood pressure (mmUg) Systolic Diastolic Mean
After placebo 82.3 (2.7) 27.8 (0.8)
26.9 (0.5)
NS NS
(4) (2) (3) (0.24)
120 (3) 88 (3) 101 (2) 6.35 (0.26)
LDL-Cholesterol (mmol.1 1)
4.21 (0.18)
4.38 (0.26)
NS
HDL-Cholesterol (mmol. 1-1)
1.18 (0.12)
1.21 (0.14)
NS
Cholesterol (mmol.l-1)
138 104 115 6.28
After nifedipine 81.8 (3.1)
P < 0.001 P < 0.001 P < 0.001 NS
Triglycerides 1.98 (0.84-4.22) 1.71 (0.85-2.69) NS (mmol.l-1)* Mean (SEM), * median and range. NS =not significant, P=significance of placebo-nifedipine difference
404
Z. Ogmiat:owska et al.: Nifedipine and platelet aggregation
Table 2. Aggregatory response after 2 weeks on placebo and 6 weeks of nifedipine treatment Parameter
After placebo
After nifedipine
%LTforADP10 (gmol.1 1) % LT for ADP 2.5 (Ixmol-1-1)
49.3 (3.2) (n : 15) 37.4 (3.6) (n = 15)
38.6 (2.5) (n : 15) 31.7 (2.8) (n = 15)
P
European,Iouma,of 1 ~ ( ~ : ~
@%QssaQ erle®9 @ Springer-Verlag 1990
Short communications
Effect of nifedipine monotherapy on platelet aggregation in patients with untreated essential hypertension* Z. Ogmia~owska 1, M. N a r t o w i c z - S t o n i e w s k a 3, J. M. S~omi/lski ~, a n d B. K r u p a - W o j c i e c h o w s k a 2 Department of Diagnostic Laboratory, 2 Second Clinic of Internal Diseases, Institute of Internal Medicine and 3 Department of Pathophysiology, Institute of Pathophysiology, Medical Academy, Gdafisk, Poland Received: April 19, 1989/Accepted in revised form: March 15, 1990
Summary. T h e effect of 6 weeks of nifedipine 30-60 mg/d on platelet aggregation and lipid p a r a m e t e r s has b e e n studied. A diminution in A D P - , adrenaline- and collagen-induced aggregation was observed. In the case of adrenaline- and collagen-stimulated aggregation the decrease was statistically significant. It was f o u n d that platelets which aggregated m a r k e d l y during the placebo t r e a t m e n t were most strongly inhibited by nifedipine. T h e changes in lipid p a r a m e t e r s were n o t significantly correlated with changes in aggregation.
Key words: nifedipine, hypertension; lipids, platelet aggregation
Calcium channel antagonists are amongst the m o s t comm o n l y used drugs in routine antihypertensive therapy. In spite of their wide applicability, the side-effects of these drugs are not fully known. T h e r e are few reports of the effects of nifedipine and b l o o d platelet function [Dale et al. 1983, N y r o p and Zweifler 1988, Walley et al. 1989]. T h e aim of the present study was to examine w h e t h e r and h o w p r o l o n g e d nifedipine t r e a t m e n t would affect platelet aggregation and lipid parameters, and what were the correlations b e t w e e n any p a r a m e t e r s affected.
30 min of supine rest. Every subject was examined by the same physician. Patients gave their informed consent to participation in the study. Nifedipine 30-60 mg/d was administered for 6 weeks after 2 weeks on placebo. The characteristics of the 15 hypertensive men under study are listed in Table 1.
Methods Blood was taken from the right antecubital vein by careful venepuncture without stasis and was collected in plastic tubes containing 1/10 volume sodium citrate (3.8%) for measurement of platelet aggregation. At the same time blood was collected for lipid tests according to the specific requirements. Platelet aggregation studies were performed using the turbidimetric method of Born [Born 1962]. Platelet rich plasma (PRP) was obtained by immediate centrifugation of the blood samples at 160 g for 10 rain at room temperature. The remaining blood was centrifuged at 3000 g for 20 min to obtain platelet poor plasma (PPP). The platelet count of the PRP was adjusted to 250-300 x 109.1- ~.An aggregometer Elvi 840 (ELVI S p.A. Milano, Italy) and Omniscribe ®recorder Logos 176 were used for this procedure. The PPP and PRP were used as 100% and 0% light transmission standards, respectively.
Table 1. Characteristics of the hypertensive patients (n = 15) Body weight (kg) Body mass index (kg.m-2)
Subjects Fifteen male patients aged 40-60 y (mean age 49.8 y) with mild to moderate untreated essential hypertension (WHO Group I -7, and Group II - 8 persons) were selected from outpatients attending the Department of Hypertension, Medical Academy of Gdafisk. The patients had no history or clinical evidence of vascular disease, diabetes mellitus, hepatic or haematological disorders. All subjects had normal urinalysis and renal function, as estimated by creatinine clearance. They were examined as outpatients and were at work. The patients were on a free diet with no restriction of sodium intake. None was addicted to alcohol or was taking any drugs. Smoking and food intake were not allowed for 12 h before sampling. The examinations were carried out between 08.30 and 09.00 h after * This rePort is a part of a project realized within the frames of the government programme of studies of the side-effects of hypotensive drugs given for i year.
Supine blood pressure (mmUg) Systolic Diastolic Mean
After placebo 82.3 (2.7) 27.8 (0.8)
26.9 (0.5)
NS NS
(4) (2) (3) (0.24)
120 (3) 88 (3) 101 (2) 6.35 (0.26)
LDL-Cholesterol (mmol.1 1)
4.21 (0.18)
4.38 (0.26)
NS
HDL-Cholesterol (mmol. 1-1)
1.18 (0.12)
1.21 (0.14)
NS
Cholesterol (mmol.l-1)
138 104 115 6.28
After nifedipine 81.8 (3.1)
P < 0.001 P < 0.001 P < 0.001 NS
Triglycerides 1.98 (0.84-4.22) 1.71 (0.85-2.69) NS (mmol.l-1)* Mean (SEM), * median and range. NS =not significant, P=significance of placebo-nifedipine difference
404
Z. Ogmiat:owska et al.: Nifedipine and platelet aggregation
Table 2. Aggregatory response after 2 weeks on placebo and 6 weeks of nifedipine treatment Parameter
After placebo
After nifedipine
%LTforADP10 (gmol.1 1) % LT for ADP 2.5 (Ixmol-1-1)
49.3 (3.2) (n : 15) 37.4 (3.6) (n = 15)
38.6 (2.5) (n : 15) 31.7 (2.8) (n = 15)
P
