Control of vascular tone in isolated mesenteric arterial segments from hypertensive patients.
1. 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. 2. Arterial constrictor responses induced by cumulative addition of Ca(2+) in the presence of noradrenaline (NA) were more effectively inhibited by the Ca(2+) 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. 3. The concentration-response curves of endothelium-dependent relaxations to acetylcholine and Ca(2+) ionophore A23187, as well as of endothelium-independent relaxations to the nitric oxide donor nitroprusside, beta-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 Ca(2+) 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). 4. These results suggest abnormal function of voltage-dependent Ca(2+) 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 Ca(2+) channels is an effective means of reducing arterial tone in essential hypertension.
Hutri-Kähönen
N
N
Medical School, Department of Pharmacological Sciences, University of Tampere, P.O. Box 607, FIN-33101 Tampere, Finland.
Kähönen
M
M
Wu
X
X
Sand
J
J
Nordback
I
I
Taurio
J
J
Pörsti
I
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology*; D008875:Middle Aged; D009129:Muscle Tonus / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D012701:Serotonin; D000001:Calcimycin; D009543:Nifedipine; D011188:Potassium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine