Control of vascular tone in isolated mesenteric arterial segments from hypertensive patients

1 Experimental hypertension is associated with several functional alteratio ns of vascular endothelium and smooth muscle, but relatively few studies ha ve examined the control of arterial tone in isolated vascular preparations from patients with essential hypertension. Therefore, we compared functiona l characteristics in vitro of distal ring segments of the mesenteric artery from 17 hypertensive and 22 normotensive humans. 2 Arterial constrictor responses induced by cumulative addition of Ca2+ in the presence of noradrenaline (NA) were more effectively inhibited by the C a2+ entry blocker nifedipine (0.5 nM) in hypertensive than normotensive sub jects (by 55.4+/-4.9, n=17 and 35.0+/-5.2%, n=22, respectively). Also the c ontractions elicited by high concentrations of KCl were more effectively in hibited 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). Howeve r, the concentration-response curves of contractions to NA, serotonin and K Cl in the absence of nifedipine were similar between the study groups. 3 The concentration-response curves of endothelium-dependent relaxations to acetylcholine and Ca2+ ionophore A23187, as well as of endothelium-indepen dent relaxations to the nitric oxide donor nitroprusside, beta-adrenoceptor agonist isoprenaline and K+ channel opener cromakalim did not show any dif ferences between the groups. Moreover, the nitric oxide synthase inhibitor N-G-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 s odium pump was evaluated by relaxations elicited by the return of K+ upon c ontractions induced by K+-free solution. The rate of K+-relaxation was simi lar in hypertensive and normotensive arteries (for all these responses n=20 -22 in the normotensive and 15-17 in the hypertensive group). 4 These results suggest abnormal function of voltage-dependent Ca2+ channel s in arterial smooth muscle of hypertensive patients, whereas vascular resp onses to endothelium-dependent and -independent vasodilators and classical contractile agents were similar between hypertensive and normotensive subje cts. The present findings support the view that blockade of voltage-depende nt Ca2+ channels is an effective means of reducing arterial tone in essenti al hypertension.