Contractions induced by potassium‐free solution and potassium relaxation in vascular smooth muscle of hypertensive and normotensive rats

Abstract

1 Vascular contractions induced by K+-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2 In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 ALM) inhibited the contractions more effectively in SHR than WKY. 3 Adrenergic denervation in vitro with 6-hydroxydopamine reduced the contractions induced by the K+-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4 The presence of intact vascular endothelium attenuated the K+-free contractions in both strains, the attenuation being smaller in SHR than WKY. N0-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 fiM), but not indomethacin (10 JM), abolished the attenuating effect of endothelium on the K+-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5 The re-addition of K+ after full K+-free contractions dose-dependently relaxed the rings. The rate of this K+-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY. 6 Vascular smooth muscle contractions induced by high concentrations of potassium were comparable between the strains. The EC50 for noradrenaline-induced contractions was lower in SHR than WKY, but the maximal forces did not differ significantly. 7 In conclusion, the contractile response in K+-free solution more clearly differentiates vascular rings from SHR and WKY than the responses induced by the classical contractile agents noradrenaline and high concentrations of potassium. The depressant effect of the presence of intact endothelium on the K+-free contractions, which was smaller in SHR than WKY, is mediated via the endothelium-derived relaxing factor. Neurotransmitter release from vascular adrenergic nerve-endings participates less in the K+-free contractile response in SHR than WKY. Moreover, the contractile response is more dependent on calcium entry through nifedipine-sensitive calcium channels in SHR than WKY. The greater K+-free contractions of denervated endothelium-denuded rings and the reduced K+ relaxation rate in SHR when compared to WKY suggest increased cell membrane permeability and decreased activity of vascular Na+, K+-ATPase, respectively, in this type of genetic hypertension.

Endothelial Modulation of Ouabain-lnduced Contraction and Sodium Pump Activity in Aortas of Normotensive Wystar-Kyoto and Spontaneously Hypertensive Rats

“…Indeed, the contractions evoked by a K+-free solution in rat mesenteric arteries [5] and those produced by ouabain in human placental arteries [6] and guinea pig carotid arteries [7] are attenuated when the endothelium is present. The endothelial factor in volved in these effects appears to be nitric oxide (NO) in rat mesenteric arteries [5], but a still unknown factor in human placental and guinea pig carotid arteries [6,7], An increase in the response to ouabain has been reported in the vasculature of spontaneously hypertensive rats (SHR) when compared with that obtained in normotensive Wistar-Kyoto rats (WKY) [8][9][10], These higher responses can be due to enhanced sodium pump activity, higher Na+-Ca2+ exchange or other alterations in mem brane permeability to Na+ and Ca2+ [8][9][10][11]. However, the possible involvement of vascular endothelium has not yet been elucidated although an important endothelial dys function associated with hypertensive disease has been reported [12], Therefore, the aim of the present work was to investi gate any involvement of vascular endothelium in the responses to ouabain in vessels from WKY and SHR, as well as the possible mechanisms involved.…”

Phosphate Binding Reduces Aortic Angiotensin-Converting Enzyme and Enhances Nitric Oxide Bioactivity in Experimental Renal Insufficiency

“…In proximal rings the endothelium was left intact, while it was denuded from the distal sample [16]. The rings were suspended between hooks in organ bath chambers (20 ml) with physiological salt solution (pH 7.4) containing (in mmol/l): NaCl 119, NaHCO 3 25, glucose 11.1, CaCl 2 1.6, KCl 4.7, KH 2 PO 4 1.2, and MgSO 4 1.2, and aerated with 95% O 2 /5% CO 2 .…”

Effect of Angiotensin II Type 1 Receptor Blockade on Conduit Artery Tone in Subtotally Nephrectomized Rats

“…In the 4 proximal rings the endothelium was left intact, and from 1 piece it was removed by gently rubbing it with a jagged injection needle [13]. The rings were suspended between hooks in an organ bath chamber in physiological salt solution (PSS; pH 7.4) containing (mmol/l): NaCl 119.0, NaHCO 3 25.0, glucose 11.1, CaCl 2 1.6, KCl 4.7, KH 2 PO 4 1.2, MgSO 4 1.2, and aerated with 95% O 2 and 5% CO 2 .…”