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The mechanisms behind renal vasodilatation elicited by stimulation of β‐adrenergic receptors are not clarified. As several classes of K channels are potentially activated, we tested the hypothesis that KV7 and BKCa channels contribute to the decreased renal vascular tone in vivo and in vitro. Changes in renal blood flow (RBF) during β‐adrenergic stimulation were measured in anaesthetized rats using an ultrasonic flow probe. The isometric tension of segmental arteries from normo‐ and hypertensive rats and segmental arteries from wild‐type mice and mice lacking functional KV7.1 channels was examined in a wire‐myograph. The β‐adrenergic agonist isoprenaline increased RBF significantly in vivo. Neither activation nor inhibition of KV7 and BKCa channels affected the β‐adrenergic RBF response. In segmental arteries from normo‐ and hypertensive rats, inhibition of KV7 channels significantly decreased the β‐adrenergic vasorelaxation. However, inhibiting BKCa channels was equally effective in reducing the β‐adrenergic vasorelaxation. The β‐adrenergic vasorelaxation was not different between segmental arteries from wild‐type mice and mice lacking KV7.1 channels. As opposed to rats, inhibition of KV7 channels did not affect the murine β‐adrenergic vasorelaxation. Although inhibition and activation of KV7 channels or BKCa channels significantly changed baseline RBF in vivo, none of the treatments affected β‐adrenergic vasodilatation. In isolated segmental arteries, however, inhibition of KV7 and BKCa channels significantly reduced the β‐adrenergic vasorelaxation, indicating that the regulation of RBF in vivo is driven by several actors in order to maintain an adequate RBF. Our data illustrates the challenge in extrapolating results from in vitro to in vivo conditions. What is the central question of this study?Does activation of KV7 or BKCa channels drive renal β‐adrenergic vasodilatation?What is the main finding and its importance?KV7 and BKCa channels contribute significantly to renal β‐adrenergic vasorelaxation in vitro but have no effect in vivo although inhibition of KV7 and BKCa channels significantly reduce baseline renal blood flow. These findings highlight the importance of in vivo studies where several different mechanisms may compensate each other. [ABSTRACT FROM AUTHOR]

Vascular conducted responses are believed to play a central role in controlling the microcirculatory blood flow. The responses most likely spread through gap junctions in the vascular wall. At present, four different connexins (Cx) have been detected in the renal vasculature, but their role in transmission of conducted vasoconstrictor signals in the preglomerular arterioles is unknown. Connexin mimetic peptides were previously reported to target and inhibit specific connexins. We, therefore, investigated whether conducted vasoconstriction in isolated renal arterioles could be blocked by the use of mimetic peptides directed against one or more connexins. Preglomerular resistance vessels were microdissected from kidneys of Sprague-Dawley rats and loaded with fura 2. The vessels were stimulated locally by applying electrical current through a micropipette, and the conducted calcium response was measured 500 [micro]m from the site of stimulation. Application of connexin mimetic peptides directed against Cx40, 37/43, 45, or a cocktail with equimolar amounts of each, did not inhibit the propagated response, whereas the nonselective gap junction uncoupler carbenoxolone completely abolished the propagated response. However, the connexin mimetic peptides were able to reduce dye coupling between rat aorta endothelial cells shown to express primarily Cx40. In conclusion, we did not observe any attenuating effects on conducted calcium responses in isolated rat interlobular arteries when exposed to connexin mimetic peptides directed against Cx40, 37/43, or 45. Further studies are needed to determine whether conducted vasoconstriction is mediated via previously undescribed pathways. vasoconstriction; conducted responses; intercellular communication

We investigated the role of large-conductance [Ca.sup.2+]-activated [K.sup.+] ([BK.sub.Ca]) channels for the basal renal vascular tone in vivo. Furthermore, the possible buffering by [BK.sub.Ca] of the vasoconstriction elicited by angiotensin II (ANG II) or norepinephrine (NE) was investigated. The possible activation of renal vascular [BK.sub.Ca] channels by cAMP was investigated by infusing forskolin. Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry or ultrasonic Doppler. Renal preinfusion of tetraethylammonium (TEA; 3.0 [micro]mol/ min) caused a small reduction of baseline RBF, but iberiotoxin (IBT; 0.3 nmol/min) did not have any effect. Renal injection of ANG II (1- 4 ng) or NE (10-40 ng) produced a transient decrease in RBF. These responses were not affected by preinfusion of TEA or IBT. Renal infusion of the [BK.sub.Ca] opener NS-1619 (90.0 nmol/min) did not affect basal RBF or the response to NE, but it attenuated the response to ANG II. Coadministration of NS-1619 with TEA or IBT abolished this effect. Forskolin caused renal vasodilation that was not inhibited by IBT. The presence of [BK.sub.Ca] channels in the preglomerular vessels was confirmed by immunohistochemistry. Despite their presence, there is no indication for a major role for [BK.sub.Ca] channels in the control of basal renal tone in vivo. Furthermore, [BK.sub.Ca] channels do not have a buffering effect on the rat renal vascular responses to ANG II and NE. The fact that NS-1619 attenuates the ANG II response indicates that the renal vascular [BK.sub.Ca] channels can be activated under certain conditions. microcirculation; vascular smooth muscle; potassium channels; Sprague-Dawley rats

We investigated :whether tempol, a superoxide dismutase mimetic, affected renal hemodynamics and arterial pressure in spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats. We also examined whether tempol affected exaggerated renal vasoconstrictor responses to ANG II in SHR. To test whether the effects of tempol were due to a restored NO system, we used the NOS inhibitor [N.sup.W]-nitro-L-arginine methyl ester (L-NAME). Renal blood flow (RBF) and mean arterial pressure (MAP) were measured in vivo by electromagnetic flowmetry and arterial catheterization in 10- to 12-wk-old anesthetized SHR and SD rats. Systolic arterial pressure (SAP) was measured in conscious rats using the tail cuff method. Tempol (1 mM) was given in the drinking water to SD (SD-T) and SHR (SHR-T) for 5-7 days for RBF measurements and for 15 days for SAP measurements. Age-matched SD (SD-C) and SHR (SHR-C) were used as controls. ANG II (1-4 ng) was administered as a bolus via a renal artery catheter. L-NAME was administered intravenously for 15-20 rain. Renal vascular resistance (RVR) was elevated in SHR-C compared with SD-C. In SHR-T, baseline RVR was not different from SD-C and SD-T rats. Tempol had no effect on RVR in SD. L-NAME elevated RVR to the same extent in all four groups. Arterial pressure was not affected by tempol. The RVR responses to ANG II were higher in SHR-C than in the SD-C group. ANG II responses were not different between SHR-T and SD-T. Overall, tempol reduced the renovascular responses to ANG II in SHR. L-NAME elevated the effects of ANG II in SD-C rats but had no effect on the ANG II responses in the other groups. Thus L-NAME treatment did not influence tempol's effects on baseline RVR or ANG II responses. We conclude that in SHR, tempol has a significant renal vasodilator effect and that it normalizes the increased renovascular ANG II sensitivity. As the effects of L-NAME are not greater in SHR-T rats, it is not likely that the elevated renal resistance and ANG II sensitivity in SHR are due to reactive oxygen speciesinduced quenching of nitric oxide. angiotensin II; hypertension; nitric oxide; oxidative stress; renal hemodynamics; spontaneously hypertensive rats

We used genistein (Gen) and tyrphostin 23 (Tyr-23) to evaluate the importance of tyrosine phosphorylation in norepinephrine (NE)-induced changes in intracellular free calcium concentration ([[[Ca.sup.2+]].sub.i]0 in rat afferent arterioles. [[[Ca.sup.2+]].sub.i] was measured in microdissected arterioles using ratiometric photometry of fura 2 fluorescence. The control [[[Ca.sup.2+]].sub.i] response to NE (t [micro]M) consisted of a rapid initial peak followed by a plateau phase sustained above baseline. Pretreatment with the tyrosine kinase inhibitor Tyr-23 (50 [micro]M, 10 rain) caused a slow 40% increase in baseline [[[Ca.sup.2+]].sub.i]. Tyr-23 attenuated peak and plateau responses to NE, both by ~70%. In the absence of extracellular [Ca.sup.2+] (0 Ca), Tyr-23 reduced the immediate [[[Ca.sup.2+]].sub.i] response to NE by ~60%, indicative of mobilization of internal stores, and abolished the plateau phase. In other arterioles, the [[[Ca.sup.2+]].sub.i] response to depolarization induced by KCl (50 [micro]M) was not attenuated by Tyr-23, indicating no direct effect on L-type [Ca.sup.2+] channels activated by depolarization. The [Ca.sup.2+] channel blocker nifedipine (1 [micro]M) inhibited the NE response by ~50%; the effects of nifedipine and Tyr-23 were not additive. Nifedipine had no inhibitory effect after Tyr-23 pretreatment, indicating Tyr-23 inhibition of [Ca.sup.2+] entry. Another tyrosine kinase inhibitor, Gen (5 and 50 [micro]M), did not affect baseline [[[Ca.sup.2+]].sub.i]. High-dose Gen inhibited the peak and plateau response to NE by 87 and 75%, respectively; low-dose Gen attenuated both responses by ~20%. In 0 Ca, Gen (50 [micro]M) abolished the immediate [[[Ca.sup.2+]].sub.i] mobilization response. Combined nifedipine and Gen (50 [micro]M) inhibited the rapid NE response by ~90% in the presence of extracellular [Ca.sup.2+]. Gen (50 [micro]M) also inhibited by 60% the [[[Ca.sup.2+]].sub.i] response to 50 mM KCl, indicating a direct interaction with voltage-sensitive, L-type [Ca.sup.2+] entry channels. These results indicate that tyrosine phosphorylation is an important link in the chain of events leading to [alpha]-adrenoceptor-induced [Ca.sup.2+] recruitment (both entry and release) in afferent arteriolar smooth muscle cells. Furthermore, different blockers of tyrosine kinase appear to have different modes of action in renal microvessels. [alpha]-adrenoceptor; renal circulation; vascular smooth muscle cells; genistein; tyrophostin 23; [Ca.sup.2+] mobilization; [Ca.sup.2+] entry; L-type [Ca.sup.2+] channels

Previous experiments from our laboratory showed that longer-lasting reductions in renal perfusion pressure (RPP) are associated with a gradual decrease in renal blood flow (RBF) that can be abolished by clamping plasma ANG II concentration ([ANG II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30-min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure ([P.sub.prox]), and proximal tubular flow rate ([Q.sub.LP]). Early distal tubular fluid conductivity was measured as an estimate of early distal [NaCl] ([[NaCl].sub.ED]), and changes in plasma renin concentration (PRC) over time were measured. During 30 min of reduced RPP, RBF decreased gradually from 6.5 [+ or -] 0.3 to 6.0 [+ or -] 0.3 ml/min after 5 min (NS) to 5.2 [+ or -] 0.2 ml/min after 30 min (P < 0.05). This decrease occurred in parallel with a gradual increase in PRC from 38.2 [+ or -] 11.0 x [10.sup.-5] to 87.1 [+ or -] 25.1 x [10.sup.-5] Goldblatt units (GU)/ml after 5 min (P < 0.05) to 158.5 [+ or -] 42.9 x [10.sup.-5] GU/ml after 30 min (P < 0.01). GFR, [P.sub.prox], and [[NaCl].sub.ED] all decreased significantly after 5 min and remained low. Estimates of pre- and postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP, both pre- and postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both pre- and postglomerular resistance due to rising plasma renin and ANG II concentrations. renal vascular resistance: autoregulation; glomerular filtration rate

The aim of the present study was to investigate the role of [Ca.sup.2+]-activated [Cl.sup.-] channels in the renal vasoconstriction elicited by angiotensin II (ANG II) and norepinephrine (NE). Renal blood flow (RBF) was measured in vivo using electromagnetic flowmetry. Ratiometric, photometry of fura 2 fluorescence was used to estimate iutracellular free [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]) in isolated preglomerular vessels from rat kidneys. Renal arterial injection of ANG II (2-4 ng) and NE (20-40 ng) produced a transient decrease in RBF. Administration orANG II ([10.sup.-7] M) and NE (5 x [10.sup.-6] M) to the isolated preglomerular vessels caused a prompt increase in [[Ca.sup.2+].sub.i]. Renal preinfusion of DIDS (0.6 and 1.25 [micro]mol/min) attenuated the ANG II-induced vasoconstriction to ~35% of the control response, whereas the effects of NE were unaltered. Niflumic acid (0.14 and 0.28 [micro]mol/min) and 2-[(2-cyclopentenyl-6,7-dichloro-2,3 -dihydro-2-methyl-1-oxo-1H-inden-5-yl)oxy]acetic acid (IAA-94; 0.045 and 0.09 [micro]mol/min) did not affect the vasoconstrictive responses of these compounds. Pretreatment with niflumic acid (50 [micro]M) or IAA-94 (30 [micro]M) for 2 min decreased baseline [[[Ca.sup.2+]].sub.i] but did not change the magnitude of the [[[Ca.sup.2+]].sub.i] response to ANG II and NE in the isolated vessels. The present results do not support the hypothesis that [Ca.sup.2+]-activated [Cl.sup.-] channels play a crucial role in the hemodynamic effects of ANG II and NE in rat renal vasculature. microcirculation; vascular smooth muscle; 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid: niflumic acid; calcium channels

The purpose of the present study was to investigate the conducted [Ca.sup.2+] response to local electrical stimulation in isolated rat interlobular arteries. Interlobular arteries were isolated from young Sprague-Dawley rats, loaded with fura 2, and attached to pipettes in a chamber on an inverted microscope. Local electrical pulse stimulation (200 ms, 100 V) was administered by means of an NaCl-filled microelectrode (0.7-1 M[OMEGA])juxtaposed to one end of the vessel. Intracellular [Ca.sup.2+] concentration ([[[Ca.sup.2+]].sub.i]) was measured with an image system at a site ~500 [micro]m from the location of the electrode. The expression of mRNA for pore-forming units Cav3.1 and Cav3.2 of voltage-sensitive T-type channels was investigated by using RT-PCR. Current stimulation elicited a conducted [[[Ca.sup.2+]].sub.i] response. A positive electrode (relative to ground) increased [[[Ca.sup.2+]].sub.i] to 145 [+ or -] 7% of baseline, whereas the response was absent when the electrode was negative. This response was not dependent on perivascular nerves, because the conducted response was unaffected by TTX (1 [micro]M). The conducted [[[Ca.sup.2+]].sub.i] response was abolished by an ambient [Ca.sup.2+] free solution and blunted by nifedipine (1 [micro]M). Rat interlobular arteries exhibited conducted [[[Ca.sup.2+]].sub.i] response to current stimulation. This response was dependent on [Ca.sup.2+] entry. L-type [Ca.sup.2+] channels may play a role in this process. microcirculation; vascular smooth muscle; hemodynamics; nifedipine; mibefradil; calcium channels

Intrarenal drug infusion plays an important role in renal experimental research. Laminar flow of the blood can cause streaming and inhomogeneous intrarenal distribution of infused drugs. We suggest a simple method to achieve a homogeneous intravascular distribution of drugs infused into the renal artery of anesthetized rats. The method employs a multiple sidehole catheter inserted into the renal artery, which enables an efficient drug mixing with the arterial blood. To verify the efficiency of this method, we use laser speckle imaging and renal artery flowmetry. The results show that, compared with the conventional single-hole catheter, the multiple sidehole catheter provides a more uniform drug distribution and a homogenous vascular response on the surface of the kidney. [ABSTRACT FROM AUTHOR]

This study provides new information about the relative importance of calcium mobilization and entry in the renal vascular response to adrenoceptor activation in afferent arterioles isolated from 7-to 8-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Intracellular free calcium concentration ([[[Ca.sup.2+]].sub.i]) was measured in microdissected arterioles utilizing ratiometric photometry of fura 2 fluorescence. There was no significant strain difference in baseline [[[Ca.sup.2+]].sub.i]. Norepinephrine (NE; [10.sup.-6] and [10.sup.-7] M) elicited immediate, sustained increases in [[[Ca.sup.2+]].sub.i]. The general temporal pattern of response to [10.sup.-6] M NE consisted of an initial peak and a maintained plateau phase. The response to NE was partially blocked by nifedipine ([10.sup.-6] M) or 8-(N,N-diethylamino) octy-13,4,5-trimetoxybenzoate (TMB-8; [10.sup.-5] M). A calcium-free external solution abolished the sustained [[[Ca.sup.2+]].sub.i] plateau response to NE, with less influence on the peak response. In the absence of calcium entry, TMB-8 ([10.sup.-5] M) completely blocked the calcium response to NE in WKY but not SHR, suggesting strain differences in mobilization. A higher concentration of TMB-8 ([10.sup.-4] M), however, blocked all discernible mobilization in both strains. We conclude that there are differences in [Ca.sup.2+] handling in renal resistance vessels between young WKY and SHR with respect to mobilization stimulated by [Alpha]-adrenoceptors. Afferent arterioles of young SHR appear to have a larger inositol-1,4,5-trisphosphatesensitive pool or release from a site less accessible to TMB-8. spontaneously hypertensive rats; Wistar-Kyoto rats; norepinephrine; hypertension; 8-(N,N-diethylamino) octyl-3,4,5-trimetoxybenzoate; nifedipine; vascular smooth muscle; inositol-1,4,5-trisphosphate-mediated mobilization; L-type calcium channel; renal circulation

[[Alpha].sub.1]-Adrenoceptor subtypes on rat afferent arterioles assessed by radioligand binding and RT-PCR. Am J Physiol Renal Physiol 281: F172-F178, 2001.--We utilized [[sup.3]H]prazosin saturation and competition radioligand binding studies to characterize the expression of [[Alpha].sub.1]-adrenoceptors in preglomerular vessels, mRNA for adrenoceptor subtypes was assayed using RT-PCR. The vessels were isolated using an iron oxide-sieving method. [[sup.3]H]prazosin bound to a single class of binding sites ([K.sub.d] 0.087 [+ or -] 0.012 nM, [B.sub.max] 326 [+ or -] 56 fmol/mg protein). Phentolamine displaced [[sup.3]H]prazosin (0.2 nM) with a p[K.sub.i] of 8.37 [+ or -] 0.09. Competition with the selective [[Alpha].sub.1A]-adrenoceptor antagonist 5-methylurapidil fit a two-site model (p[K.sub.i] 9.38 [+ or -] 0.21 and 7.04 [+ or -] 0.15); 59 [+ or -] 3% of the sites were high-affinity, and 41 [+ or -] 3% were low-affinity binding sites. Competition with the [[Alpha].sub.1D]-adrenoceptor antagonist 8-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-8-azaspiro-[4.5]decane-7, 9-dione dihydrochloride (BMY-7378) fit a one-site model with low affinity (p[K.sub.i] 6.83 [+ or -] 0.03). The relative contents of [[Alpha].sub.1A]-, [[Alpha].sub.1B]-, and [[Alpha].sub.1D]-adrenoceptor mRNAs were 64 [+ or -] 5, 25 [+ or -] 5, and 11 [+ or -] 1%, respectively. Thus there was a very good correlation between mRNA and receptor binding for the subtypes. These data indicate a predominance of the [[Alpha].sub.1A]-adrenoceptor subtype in rat renal resistance vessels, with smaller densities of [[Alpha].sub.1B]- and [[Alpha].sub.1D]-adrenoceptors. renal circulation; vascular smooth muscle; reverse transcription-polymerase chain reaction; mRNA; renal nerve; catecholamine

Conducted vasoconstriction in rat mesenteric arterioles: role for dihydropyridine-insensitive [Ca.sup.2+] channels. Am J Physiol Heart Circ Physiol 280: H582-H590, 2001.--The aim of this study was to evaluate the role of voltage-operated [Ca.sup.2+] channels in the initiation and conduction of vasoconstrictor responses to local micropipette electrical stimulation of rat mesenteric arterioles (28 [+ or -] 1 [micro]m, n = 79) in vivo. Local and conducted (600 [micro]m upstream from the pipette) vasoconstriction was not blocked by TTX (1 [micro]mol/l, n = 5), nifedipine, or nimodipine (10 [micro]mol/l, n = 9). Increasing the [K.sup.+] concentration of the superfusate to 75 mmol/l did not evoke vasoconstriction, but this depolarizing stimulus reversibly abolished vasoconstrictor responses to current stimulation (n = 7). Addition of the T-type [Ca.sup.2+] antagonist mibefradil (10 [micro]mol/l, n = 6) to the superfusate reversibly blocked local and conducted vasoconstriction to current stimulation. With the use of RT-PCR techniques, it was demonstrated that rat mesenteric arterioles [is less than] 40 [micro]m do not express mRNA for L-type [Ca.sup.2+] channels ([[Alpha].sub.1C]-subunit), whereas mRNA coding for T-type subunits was found ([[Alpha].sub.1G]- and [[Alpha].sub.1H]-subunits). The data indicate that L-type [Ca.sup.2+] channels are absent from rat mesenteric arterioles ([is less than] 40 [micro]m). Rather, the vasoconstrictor responses appear to rely on other types of voltage-gated, dihydropyridine-insensitive [Ca.sup.2+] channels, possibly of the T-type. L-type [Ca.sup.2+] channels; T-type [Ca.sup.2+] channels; mibefradil; [Ca.sup.2+] channel antagonists; RT-PCR

Salomonsson, Max, Kristina Brannstrom, and William J. Arendshorst. [[Alpha].sub.1]-Adrenoceptor subtypes in rat renal resistance vessels: in vivo and in vitro studies. Am. J. Physiol. Renal Physiol. 278: F138-F147, 2000.--This study provides new information about the relative importance of different [[Alpha].sub.1]-adrenoceptors during norepinephrine (NE) activation in rat renal resistance vessels. In Sprague-Dawley rats, we measured renal blood flow (RBF) using electromagnetic flowmetry in vivo and the intracellular free calcium concentration ([[[Ca.sup.2]+].sub.i]) utilizing ratiometric photometry of fura 2 fluorescence in isolated afferent arterioles. Renal arterial bolus injection of NE produced a transient 46% decrease in RBF. In microdissected afferent arterioles, NE (1 [micro]M) elicited an immediate square-shaped increase in [[[Ca.sup.2+]].sub.i], from 90 to 175 nM (P [is less than] 0.001). Chloroethylclonidine (CEC) (50 [micro]M) had no chronic irreversible alkylating effect in vitro but exerted acute reversible blockade on norepinephrine (NE) responses both on [[[Ca.sup.2+]].sub.i] in vitro and on RBF invivo. The RBF response was attenuated by ~50% by the putative [[Alpha].sub.1A]-adrenoceptor and [[Alpha].sub.1D]-adrenoceptor antagonists 5-methylurapidil (5-MU), and 8- [2- [4-(2-methoxyphenyl)-1-piperazinyl] ethyl] -8-azaspiro [4.5]decane-7,9-dione dihydrochloride (BMY-7378) (12.5 and 62.5 [micro]g/h), respectively. The in vitro [[[Ca.sup.2+]].sub.i] response to NE was blocked ~25% and 50% by 5-MU (100 nM and 1 [micro]M). BMY-7378 (100 nM and 1 [micro]M) attenuated the NE-induced response by ~40% and 100%. The degree of inhibition in vitro was similar to the in vivo experiments. In conclusion, 5-MU and BMY-7378 attenuated the NE-induced responses, although relatively high concentrations were required, suggesting involvement of both the [[Alpha].sub.1A]-adrenoceptor and [[Alpha].sub.1D]-adrenoceptor. Participation of the [[Alpha].sub.1B]-adrenoceptor is less likely, as we found no evidence for CEC-induced alkylation. norepinephrine; [[Alpha].sub.1A]-adrenoceptor; [[Alpha].sub.1B]-adrenoceptor; [[Alpha].sub.1D]-adrenoceptor; renal circulation; afferent arteriole; calcium; vascular smooth muscle

Abdominal obesity and/or a high intake of fructose may cause hypertension. K+ channels, Na/K-ATPase, and voltage-gated Ca2+ channels are crucial determinants of resistance artery tone and thus the control of blood pressure. Limited information is available on the role of K+ transporters in long-term diet-induced hypertension in rats. We hypothesized that a 28-week diet rich in fat, fructose, or both, will lead to changes in K+ transporter expression and function, which is associated with increased blood pressure and decreased arterial function. Male Sprague–Dawley (SD) rats received a diet containing normal chow (Control), high-fat chow (High Fat), high-fructose in drinking water (High Fructose), or a combination of high-fat and high-fructose diet (High Fat/Fruc) for 28 weeks from the age of 4 weeks. Measurements included body weight (BW), systolic blood pressure (SBP), mRNA expression of vascular K+ transporters, and vessel myography in small mesenteric arteries (SMAs). BW was increased in the High Fat and High Fat/Fruc groups, and SBP was increased in the High Fat/Fruc group. mRNA expression of small conductance calcium-activated K+ channel (SKCa), intermediate conductance calcium-activated K+ (IKCa), and Kir2.1 inward rectifier K+ channels were reduced in the High Fat/Fruc group. Reduced endothelium-derived hyperpolarization (EDH)-type relaxation to acetylcholine (ACh) was seen in the High Fat and High Fat/Fruc groups. Ba2+-sensitive dilatation to extracellular K+ was impaired in all the experimental diet groups. In conclusion, reduced expression and function of SKCa, IKCa, and Kir2.1 channels are associated with elevated blood pressure in rats fed a long-term High Fat/Fruc. Rats fed a 28-week High Fat/Fruc provide a relevant model of diet-induced hypertension. [ABSTRACT FROM AUTHOR]