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Aortic coarctation: The in vitro response to noradrenalin, potassium and prostaglandin F2α in intercostal arteries
Gen. Pharmac. Vol. 14, pp. 155 to 156, 1983
0306-3623/83/010155-02503.00/0 Copyright © 1983 Pergamon Press Ltd
Printed in Great Britain. All rights reserved
AORTIC COARCTATION: THE IN V I T R O R E S P O N S E TO NORADRENALIN, POTASSIUM AND PROSTAGLANDIN F2~ IN INTERCOSTAL ARTERIES JENS SEHESTEDand ERICH MIKKELSEN The University Clinic of Cardiovascular Surgery, Aarhus Kommunehospital and The Institute of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark (Received 19 April 1982)
Abstract--By applying the ring-method for the determination of isometric contraction force in intercostal arteries, it has been found that patients with aortic coarctation have an apparently selective loss of c~-receptors which is not found in normotensive controls. Combined with the functional and structural alterations found in the precoarctational aorta and the natural history of the blood pressure development the results from the intercostal arteries are suggested further to emphasize the adaptive character of coarctational hypertension.
Pharmacodynamic studies have shown a significantly reduced contractility in ring preparations obtained from the prestenotic segment of the aorta in human coarctation when compared with the aorta from below the coarctation (Sehested et al., 1982). This has been atributed to the larger volumefraction of collagen and the smaller fraction of smooth-muscle mass found (by morphometric assessment) in the precoarctational segment of the aorta in comparison with the aorta distal to the stenosis and with the aorta from normal, age-matched controls. No differences have been found regarding the amount of elastin from the various aortic segments (Sehested et al., 1982). These results have been regarded as evidence of the precoarctational aorta being more rigid--and thus less distensable--than the aorta from below the coarctation and from normal, age-matched aortas. This might influence the stretching of the baroreceptors (mainly located central to the "typical" coarctation) being less than if located in an aorta with normal distensability. The result would be a maintained precoarctational hypertension without the necessity of involving hormonal systems as the renin-angiotensin aldosterone system. In contrast to for example essential hypertension, a malignant development is extremely rare--if ever seen--in the hypertension associated with coarctation. It only happens as the "postoperative paradoxical hypertension". This emphasizes the adaptive character of coarctational hypertension and is further illustrated by the development in blood pressure rise which almost fades away between the ages of 20 and 30 years (Campbell & Baylis, 1956); a period in which the large majority of patients has grown out. In order to investigate other areas of the vascular bed in patients with coarctation we studied the pharmacodynamical response to potassium (K+), noradrenaline (NA) and prostaglandin F2~ (PGF) in intercostal arteries from patients and normotensive controls. 155
MATERIALS AND METHODS Intercostal arteries were obtained from 6 children and young adults undergoing surgery for an isolated aortic coarctation. The determination of isometric contractions was carried out by the ring-method previously described (Sehested et al., 1982; Mikkelsen et al., 1978) and supramaximal doses of K + (127 mM), NA (18 #M) and PGF2~ (28 gM) were used as in the study concerning the coarctated aortas (Sehested et al., 1982). An identical procedure was applied to intercostal arteries from 6 normotensive, though older, patients who had thoracotomies performed because of lung tumors.
RESULTS No statistically significant difference was found between the mean response to K ÷ and P G F in the two groups. Furthermore, the mean response to NA was also similar to that of K ÷ in the controls (NA: 95 + 6~o of K÷). In patients with coarctation, however, the contractile response to NA was always found considerably reduced when compared with that of K ÷ (and PGF) being only 50 + 2.4~o of the response to potassium (Fig. 1).
DISCUSSION Since it was not possible to obtain an age matched control series, the patients and normotensives served as their own controls, i.e. for each artery the responses to NA and P G F were compared with the contractions induced by potassium. Contrary to the aorta central to the coarctation, which showed a reduced contractile response to all 3 agents used, when compared with the aorta distal to the stenosis (Sehested et al., 1982), the intercostal arteries from these patients showed a selective loss of reactivity to NA. This suggests a loss of receptors and not of smooth-muscle mass as in the precoarctational aorta.
156
lg
JENS SEHESTEDand ERICH MIKKELSEN
IF:. +
+
+
K+
NA
F2o
,olJ 3 +
+
K+
NA
f +
Fza
IOmin
Fig. 1. The contractile response to potassium (127 mM), noradrenaline (18 #M) and prostaglandin F2, (28/~M) in intercostal arteries from a patient with aortic coarctation (upper row) and a normotensive control (lower row).
As the intercostal arteries in coarctation play a major role in the collateral circulation, it is tempting to regard the apparently selective loss of ct-receptors as an adaptive p h e n o m e n o n , a v o i d i n ~ i n this context an unfortunate vaso-constriction during periods with high plasma levels of catecholamines, as for instance during lower limb work.
REFERENCES
CAMPBELL M. & BAYLISJ. H. (1956) The course and prognosis of coarctation of the aorta. Br. Heart J. 18, 475-495. MIKKELSEN E., ANDERSSON K. E. • BENGTSSON B. (1978) Effects of verapamil and nitroglycerin on contractile responses to potassium and noradrenaline in isolated human peripheral veins. Acta pharmac, tox. 42, 14-22. SEHESTED J., BAANDRUPU. & MIKKELSEN E. (1982) Different reactivity and structure of pre- and poststenotic aorta in human coarctation. Implications for baroreceptorfunction. Circulation 65, 1060-1065.
0306-3623/83/010155-02503.00/0 Copyright © 1983 Pergamon Press Ltd
Printed in Great Britain. All rights reserved
AORTIC COARCTATION: THE IN V I T R O R E S P O N S E TO NORADRENALIN, POTASSIUM AND PROSTAGLANDIN F2~ IN INTERCOSTAL ARTERIES JENS SEHESTEDand ERICH MIKKELSEN The University Clinic of Cardiovascular Surgery, Aarhus Kommunehospital and The Institute of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark (Received 19 April 1982)
Abstract--By applying the ring-method for the determination of isometric contraction force in intercostal arteries, it has been found that patients with aortic coarctation have an apparently selective loss of c~-receptors which is not found in normotensive controls. Combined with the functional and structural alterations found in the precoarctational aorta and the natural history of the blood pressure development the results from the intercostal arteries are suggested further to emphasize the adaptive character of coarctational hypertension.
Pharmacodynamic studies have shown a significantly reduced contractility in ring preparations obtained from the prestenotic segment of the aorta in human coarctation when compared with the aorta from below the coarctation (Sehested et al., 1982). This has been atributed to the larger volumefraction of collagen and the smaller fraction of smooth-muscle mass found (by morphometric assessment) in the precoarctational segment of the aorta in comparison with the aorta distal to the stenosis and with the aorta from normal, age-matched controls. No differences have been found regarding the amount of elastin from the various aortic segments (Sehested et al., 1982). These results have been regarded as evidence of the precoarctational aorta being more rigid--and thus less distensable--than the aorta from below the coarctation and from normal, age-matched aortas. This might influence the stretching of the baroreceptors (mainly located central to the "typical" coarctation) being less than if located in an aorta with normal distensability. The result would be a maintained precoarctational hypertension without the necessity of involving hormonal systems as the renin-angiotensin aldosterone system. In contrast to for example essential hypertension, a malignant development is extremely rare--if ever seen--in the hypertension associated with coarctation. It only happens as the "postoperative paradoxical hypertension". This emphasizes the adaptive character of coarctational hypertension and is further illustrated by the development in blood pressure rise which almost fades away between the ages of 20 and 30 years (Campbell & Baylis, 1956); a period in which the large majority of patients has grown out. In order to investigate other areas of the vascular bed in patients with coarctation we studied the pharmacodynamical response to potassium (K+), noradrenaline (NA) and prostaglandin F2~ (PGF) in intercostal arteries from patients and normotensive controls. 155
MATERIALS AND METHODS Intercostal arteries were obtained from 6 children and young adults undergoing surgery for an isolated aortic coarctation. The determination of isometric contractions was carried out by the ring-method previously described (Sehested et al., 1982; Mikkelsen et al., 1978) and supramaximal doses of K + (127 mM), NA (18 #M) and PGF2~ (28 gM) were used as in the study concerning the coarctated aortas (Sehested et al., 1982). An identical procedure was applied to intercostal arteries from 6 normotensive, though older, patients who had thoracotomies performed because of lung tumors.
RESULTS No statistically significant difference was found between the mean response to K ÷ and P G F in the two groups. Furthermore, the mean response to NA was also similar to that of K ÷ in the controls (NA: 95 + 6~o of K÷). In patients with coarctation, however, the contractile response to NA was always found considerably reduced when compared with that of K ÷ (and PGF) being only 50 + 2.4~o of the response to potassium (Fig. 1).
DISCUSSION Since it was not possible to obtain an age matched control series, the patients and normotensives served as their own controls, i.e. for each artery the responses to NA and P G F were compared with the contractions induced by potassium. Contrary to the aorta central to the coarctation, which showed a reduced contractile response to all 3 agents used, when compared with the aorta distal to the stenosis (Sehested et al., 1982), the intercostal arteries from these patients showed a selective loss of reactivity to NA. This suggests a loss of receptors and not of smooth-muscle mass as in the precoarctational aorta.
156
lg
JENS SEHESTEDand ERICH MIKKELSEN
IF:. +
+
+
K+
NA
F2o
,olJ 3 +
+
K+
NA
f +
Fza
IOmin
Fig. 1. The contractile response to potassium (127 mM), noradrenaline (18 #M) and prostaglandin F2, (28/~M) in intercostal arteries from a patient with aortic coarctation (upper row) and a normotensive control (lower row).
As the intercostal arteries in coarctation play a major role in the collateral circulation, it is tempting to regard the apparently selective loss of ct-receptors as an adaptive p h e n o m e n o n , a v o i d i n ~ i n this context an unfortunate vaso-constriction during periods with high plasma levels of catecholamines, as for instance during lower limb work.
REFERENCES
CAMPBELL M. & BAYLISJ. H. (1956) The course and prognosis of coarctation of the aorta. Br. Heart J. 18, 475-495. MIKKELSEN E., ANDERSSON K. E. • BENGTSSON B. (1978) Effects of verapamil and nitroglycerin on contractile responses to potassium and noradrenaline in isolated human peripheral veins. Acta pharmac, tox. 42, 14-22. SEHESTED J., BAANDRUPU. & MIKKELSEN E. (1982) Different reactivity and structure of pre- and poststenotic aorta in human coarctation. Implications for baroreceptorfunction. Circulation 65, 1060-1065.