Enhanced single-channel K+ current in arterial membranes from genetically hypertensive rats

England, Sarah K.; Wooldridge, Theresa A.; Stekiel, William J.; Rusch, Nancy J.

doi:10.1152/ajpheart.1993.264.5.h1337

Cited by 61 publications

(67 citation statements)

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“…The contractions evoked by TEA, iberiotoxin, or charybdotoxin were significantly higher in SHR MA than in WKY, suggesting an increased functional activity of K Ca channels in the SHR vessels. This is consistent with the report by Rusch et al (1992) in SHR aorta and that by Asano and Nomura (2002) in SHR femoral, mesenteric, and carotid artery, and in SHR aortic smooth muscle cells (England et al, 1993). In a separate study, we have performed a Western blot analysis of the large conductance K Ca channel protein in the MA from SHR and WKY, and found that K Ca was increased in SHR (unpublished data), similar to a previous report using SHR aorta (Liu et al, 1997).…”

Section: Discussionsupporting

confidence: 94%

Vascular relaxation response to hydrogen peroxide is impaired in hypertension

Gao

Zhang

Hirota

et al. 2004

British J Pharmacology

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1 In phenylephrine (1 mM)-precontracted rat superior mesenteric arteries (MA), hydrogen peroxide (H 2 O 2 , 0.3 and 1 mM) caused a biphasic response: a transient contraction followed by a relaxation. In the presence of thromboxane A 2 /prostaglandin H 2 (TP) receptor antagonist (SQ 29548), the contractile component of the biphasic response was abolished. The relaxation response to H 2 O 2 was smaller in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). 2 The mechanisms for the attenuated relaxation to H 2 O 2 in the SHR were studied. KCl (40 mM) prevented the relaxation response. Calcium-dependent K þ channel (K Ca ) blockers (tetraethylammonium chloride, TEA; iberiotoxin, and charybdotoxin) showed a greater inhibition of H 2 O 2 relaxation in SHR than in WKY, whereas voltage-dependent K þ -channel (K v ) blocker 4-aminopyridine was more effective in inhibiting the relaxation in WKY than in SHR. 3 H 2 O 2 (1 mM) greatly enhanced the frequency and intensity of the spontaneous transient outward K þ currents in SHR MA, and the effects of H 2 O 2 were inhibited by iberiotoxin, while in WKY MA the K þ currents induced by H 2 O 2 were mainly of the K v type. The consequence of the activation of different types of K þ channel was that the net increase in mean outward K þ current density in response to H 2 O 2 was smaller in SHR than in WKY, which may account for the attenuated relaxation response to H 2 O 2 in the SHR. 4 The contractile responses of MA to TEA, iberiotoxin, and charybdotoxin were greater in SHR than in WKY. 5 In summary, an attenuated relaxation response to H 2 O 2 was found in SHR MA when compared to WKY. In contrast to the activation of K v channels in WKY, H 2 O 2 markedly enhanced K Ca activity in SHR, resulting in an attenuation of the increase in mean outward K þ current density in response to H 2 O 2 . These results suggest that alteration in K þ channel activation by reactive oxygen species may play a role in the development of hypertension in SHR.

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Section: Discussionsupporting

confidence: 94%

Vascular relaxation response to hydrogen peroxide is impaired in hypertension

Gao

Zhang

Hirota

et al. 2004

British J Pharmacology

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“…Our finding that the altered membrane potential observed in SHR carotids is not due to impaired K ϩ channels agrees with previous reports based on patch-clamp measurements of K ϩ currents in SHR 18 and in aldosterone-induced hypertensive rats 19 . However, these findings contrast with a report of decreased K Ca currents in angiotensin-induced hypertension 20 .…”

Section: Discussionsupporting

confidence: 93%

Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR

et al. 2004

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Abstract-We examined the roles played by impaired K ϩ channels, diminished nitric oxide (NO) production, endothelin release, and smooth muscle membrane potential in the increased restenosis observed in spontaneously hypertensive rat (SHR) carotid arteries after angioplasty. The SHR carotid was found to be less polarized than that of normotensive Wistar rats (NWR), and it was further depolarized by the ␣ 2 agonist UK 14,304. This response was blocked by iberiotoxin, indicating that calcium-dependent K ϩ channels operate normally in the SHR carotid. Acetylcholine caused a hyperpolarization that was significantly smaller in SHR than in NWR carotids, indicating a deficient release of NO in the SHR. After angioplasty, SHR and NWR vessels were depolarized, returning to baseline after 10 days. In the SHR but not in the NWR the contralateral carotid was also depolarized, and this was prevented by the endothelin A/B receptor antagonist bosentan. After angioplasty, endothelin-1 plasma levels increased in both SHR and NWR, but the increase was significantly more prolonged in SHR. We found that the more pronounced restenosis observed in the SHR carotid after angioplasty is not due to impairment of calcium-dependent K ϩ channels but is related to the relatively depolarized vascular smooth muscles, involving endothelin release caused by reduced NO levels in that strain. Key Words: rats, spontaneously hypertensive Ⅲ angioplasty Ⅲ carotid arteries Ⅲ muscle smooth, vascular Ⅲ membranes Ⅲ endothelin T he vascular endothelium plays a role in blood flow control through the release of relaxant and contractile factors. Thus, to prevent overactivation of contractile responses, it releases relaxant factors such as endotheliumderived hyperpolarizing factor, prostanoids, and nitric oxide (NO). The endothelium also prevents the development of vascular lesions by inhibiting platelet aggregation, leukocyte adhesion, and proliferation of vascular smooth muscle cells. 1 This protective role is altered in pathological conditions such as arterial hypertension, which is characterized by cell permeability changes, leukocyte adhesion, and smooth muscle cell proliferation. Also, the repair mechanism designed to restore the vessel wall after damage from different causes frequently escapes self-limiting control, resulting in lumen narrowing caused by smooth muscle cell proliferation. These processes are the precursors of atherosclerotic plaque formation, which leads to increased vascular resistance and to restenosis. 2 Procedures such as atherectomy performed by balloon injury (angioplasty) widen the lumen but cause extensive endothelium destruction, leaving the vascular wall without protection. This injury stimulates medial smooth muscle cell proliferation and migration to the deendothelized surface to form a neointima. Neointima proliferation and subsequent vascular restenosis are believed to be the main events in the initiation of the atherosclerosis that limits the long-term efficacy of percutaneous transluminal coronary angioplasty. 3 It is well...

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“…79 Only recently, however, has the TEA-sensitive, Ca 2+ -activated "maxi-K + channel" been identified as the likely molecular pathway for this elevated current. 8 At the same membrane potential and [Ca],, this K + channel type appears to show a higher open state probability in cell-attached and inside-out aortic membrane patches from adult SHR compared with WKY rats. 8 However, despite clarification of its single-channel nature, the link between high blood pressure and the etiology of elevated arterial K + current remains unclear.…”

Section: Discussionmentioning

confidence: 87%

“…8 At the same membrane potential and [Ca],, this K + channel type appears to show a higher open state probability in cell-attached and inside-out aortic membrane patches from adult SHR compared with WKY rats. 8 However, despite clarification of its single-channel nature, the link between high blood pressure and the etiology of elevated arterial K + current remains unclear. With regard to genetic hypertension, only K + flux in vascular membranes from adult SHR has been measured, 5 and therefore it is unknown whether K + channel changes are a consequence of elevated blood pressure or precede blood pressure elevation as an expression of genetic diversity between rat strains.…”

Section: Discussionmentioning

confidence: 87%

“…This drug preferentially blocks maxi-K + channels over other K + channel types, 71013 with 2 mmol/L TEA reducing single-channel maxi-K + current by 75% to 90% in this preparation. 8 Experiments were based on the premise that the presence of TEA-induced arterial contraction indicated a high level of maxi-K + channel current, whereas the absence of TEA responsiveness indicated reduced maxi-K + channel opening. 7 -9 With this in mind, recordings in Fig 2A show that TEA (0.1 to 5 mmol/L) induced only small constrictions in untreated and ramipril-treated WKY aortas but dose-dependently contracted aortas of untreated SHR.…”

Section: Effect Of Tetraethylammonium On Basal Tensionmentioning

confidence: 99%

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Remission of high blood pressure reverses arterial potassium channel alterations.

Rusch

Runnells

1994

Hypertension

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Rat arterial muscle cells show an elevated Ca 2+ -dependent K + efflux during the established phase of hypertension. This association of enhanced K + efflux with high arterial pressure implies that changes of in vivo blood pressure can alter the level of K + channel current in arterial membranes. We directly tested this hypothesis by comparing K + current density between patch-clamped aortic muscle membranes of normotensive Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR), and SHR treated with the angiotensin-converting enzyme inhibitor ramipril (3.5 mg/kg per day PO) to normalize blood pressure. Peak macroscopic K + current was measured during progressive depolarizing steps (10 mV) from -60 and +60 mV in cells diaryzed with pipette solution containing 10" 6 mol/L calcium to amplify Ca 2+ -dependent K + current. With the use of this approach, maximum K + current density in aortic muscle membranes of untreated SHR was 2.6-fold higher than in untreated WKY rats (SHR, 31 ±3 pA/pF; WKY, 12±1 pA/pF) C alcium-dependent K + efflux is increased in arteries from genetic and renal rat models of established hypertension.1 -6 It has been proposed that this enhanced K + current is a consequence of high blood pressure and is a compensatory mechanism activated during the development of hypertension to counteract arterial excitability and prevent further vasoconstriction. 79 However, increased arterial K + current has been described only in the established phase of hypertension, 5 and there is little direct evidence to link changes in blood pressure amplitude with dynamic modulation of K + current levels in arterial muscle membranes.To explore the relation between blood pressure changes and arterial K + current density, we compared K + current density between patch-clamped aortic muscle cell membranes of adult spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) rats, and SHR after antihypertensive treatment with the angiotensin-converting enzyme inhibitor ramipril. In addition, parallel measurements of tension were recorded in isolated vessel rings to determine whether K + current suppressed aortic contraction in these preparations. Thus, we investigated for the first time whether a potential link exists between blood pressure regression and modulation of K + current in arterial muscle membranes of hypertensive rats.From the Department of Physiology, Medical College of Wisconsin, Milwaukee.Correspondence to Nancy J. Rusch, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, Wl 53226. and was predominantly blocked by 2 mmol/L tetraethylammonium. K + current density in SHR aortic membranes was unchanged after 1 week of ramipril therapy, but it was reduced 42% (to 18±1 pA/pF) after 2 weeks of treatment. Parallel tensionrecording studies showed that untreated SHR aortic segments but not aortic segments from WKY rats or ramipril-treated SHR constricted strongly after block of Ca 2+ -dependent K + channels by tetraethylammonium. Our findings imply...

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Enhanced single-channel K+ current in arterial membranes from genetically hypertensive rats

Cited by 61 publications

References 0 publications

Vascular relaxation response to hydrogen peroxide is impaired in hypertension

Vascular relaxation response to hydrogen peroxide is impaired in hypertension

Role of Membrane Potential and Expression of Endothelial Factors in Restenosis After Angioplasty in SHR

Remission of high blood pressure reverses arterial potassium channel alterations.

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