Article date: August 1999
By: Nina Hutri‐Kähönen, Mika Kähönen, Xiumin Wu, Juhani Sand, Isto Nordback, Jyrki Taurio, Ilkka Pörsti, in Volume 127, Issue 7, pages 1735-1743
Experimental hypertension is associated with several functional alterations of vascular endothelium and smooth muscle, but relatively few studies have examined the control of arterial tone in isolated vascular preparations from patients with essential hypertension. Therefore, we compared functional characteristics in vitro of distal ring segments of the mesenteric artery from 17 hypertensive and 22 normotensive humans.
Arterial constrictor responses induced by cumulative addition of Ca2+ in the presence of noradrenaline (NA) were more effectively inhibited by the Ca2+ entry blocker nifedipine (0.5 nM) in hypertensive than normotensive subjects (by 55.4±4.9, n=17 and 35.0±5.2%, n=22, respectively). Also the contractions elicited by high concentrations of KCl were more effectively inhibited by nifedipine in arterial rings from hypertensive than normotensive patients (by 38.9±3.7, n=17 and 20.2±4.6%, n=22, respectively). However, the concentration‐response curves of contractions to NA, serotonin and KCl in the absence of nifedipine were similar between the study groups.
The concentration‐response curves of endothelium‐dependent relaxations to acetylcholine and Ca2+ ionophore A23187, as well as of endothelium‐independent relaxations to the nitric oxide donor nitroprusside, β‐adrenoceptor agonist isoprenaline and K+ channel opener cromakalim did not show any differences between the groups. Moreover, the nitric oxide synthase inhibitor NG‐nitro‐L‐arginine methyl ester (0.1 mM) almost abolished the relaxations to acetylcholine and Ca2+ ionophore in both groups, indicating that these responses were largely mediated by nitric oxide. The function of arterial sodium pump was evaluated by relaxations elicited by the return of K+ upon contractions induced by K+‐free solution. The rate of K+‐relaxation was similar in hypertensive and normotensive arteries (for all these responses n=20–22 in the normotensive and 15–17 in the hypertensive group).
These results suggest abnormal function of voltage‐dependent Ca2+ channels in arterial smooth muscle of hypertensive patients, whereas vascular responses to endothelium‐dependent and ‐independent vasodilators and classical contractile agents were similar between hypertensive and normotensive subjects. The present findings support the view that blockade of voltage‐dependent Ca2+ channels is an effective means of reducing arterial tone in essential hypertension.
Experimental hypertension is associated with several functional alterations of vascular endothelium and smooth muscle, but relatively few studies have examined the control of arterial tone in isolated vascular preparations from patients with essential hypertension. Therefore, we compared functional characteristics in vitro of distal ring segments of the mesenteric artery from 17 hypertensive and 22 normotensive humans.
Arterial constrictor responses induced by cumulative addition of Ca2+ in the presence of noradrenaline (NA) were more effectively inhibited by the Ca2+ entry blocker nifedipine (0.5 nM) in hypertensive than normotensive subjects (by 55.4±4.9, n=17 and 35.0±5.2%, n=22, respectively). Also the contractions elicited by high concentrations of KCl were more effectively inhibited by nifedipine in arterial rings from hypertensive than normotensive patients (by 38.9±3.7, n=17 and 20.2±4.6%, n=22, respectively). However, the concentration‐response curves of contractions to NA, serotonin and KCl in the absence of nifedipine were similar between the study groups.
The concentration‐response curves of endothelium‐dependent relaxations to acetylcholine and Ca2+ ionophore A23187, as well as of endothelium‐independent relaxations to the nitric oxide donor nitroprusside, β‐adrenoceptor agonist isoprenaline and K+ channel opener cromakalim did not show any differences between the groups. Moreover, the nitric oxide synthase inhibitor NG‐nitro‐L‐arginine methyl ester (0.1 mM) almost abolished the relaxations to acetylcholine and Ca2+ ionophore in both groups, indicating that these responses were largely mediated by nitric oxide. The function of arterial sodium pump was evaluated by relaxations elicited by the return of K+ upon contractions induced by K+‐free solution. The rate of K+‐relaxation was similar in hypertensive and normotensive arteries (for all these responses n=20–22 in the normotensive and 15–17 in the hypertensive group).
These results suggest abnormal function of voltage‐dependent Ca2+ channels in arterial smooth muscle of hypertensive patients, whereas vascular responses to endothelium‐dependent and ‐independent vasodilators and classical contractile agents were similar between hypertensive and normotensive subjects. The present findings support the view that blockade of voltage‐dependent Ca2+ channels is an effective means of reducing arterial tone in essential hypertension.
British Journal of Pharmacology (1999) 127, 1735–1743; doi:10.1038/sj.bjp.0702716
DOI: 10.1038/sj.bjp.0702716
View this article