Functional activity of Ca2+-dependent K+ channels is increased in basilar artery during chronic hypertension

1997 ◽  
Vol 272 (3) ◽  
pp. H1287-H1291 ◽  
Author(s):  
R. Paterno ◽  
D. D. Heistad ◽  
F. M. Faraci
Keyword(s):  
Arterial Pressure ◽  
Basilar Artery ◽  
Vessel Diameter ◽  
Chronic Hypertension ◽  
Spontaneously Hypertensive ◽  
K Channels ◽  
Cranial Window ◽  
Wistar Kyoto ◽  
Oxide Synthase

We examined the hypothesis that activity of Ca2+-dependent K+ channels is increased in the basilar artery during chronic hypertension. Diameter of the basilar artery was measured using a cranial window in anesthetized normotensive Wistar-Kyoto rats (WKY, arterial pressure = 109 +/- 3 mmHg, mean +/- SE) and stroke-prone spontaneously hypertensive rats (SHRSP, arterial pressure = 179 +/- 4 mmHg). Responses of the basilar artery to topical application of tetraethylammonium ion (TEA), an inhibitor of Ca2+-dependent K+ channels, were examined in WKY and SHRSP. Vessel diameter decreased by 2 +/- 1 and 4 +/- 0.1% in WKY and by 7 +/- 2 and 18 +/- 1% in SHRSP (P < 0.05 vs. WKY) in response to 10(-4) and 10(-3) M TEA, respectively. Similar results were obtained using iberiotoxin (10(-8) and 10(-7) M), a highly selective inhibitor of Ca2+-dependent K+ channels. In contrast to constrictor responses to TEA and iberiotoxin, constrictor responses of the basilar artery in response to serotonin and U-46619 were similar in WKY and SHRSP. In WKY rats that were made chronically hypertensive (arterial pressure = 172 +/- 6 mmHg) after treatment for 4 wk with N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, constriction of the basilar artery in response to TEA was also enhanced. These findings suggest that activity of Ca2+-dependent K+ channels is enhanced in the basilar artery in vivo in two models of chronic hypertension. Thus Ca2+-dependent K+ channels in the basilar artery may be activated during chronic hypertension, perhaps as a response to elevation of intracellular concentration of Ca2+.

Role of ATP-sensitive K+ channels in CGRP-induced dilatation of basilar artery in vivo

1993 ◽  
Vol 265 (2) ◽  
pp. H581-H585 ◽  
Author(s):  
T. Kitazono ◽  
D. D. Heistad ◽  
F. M. Faraci
Keyword(s):  
Basilar Artery ◽  
Minor Component ◽  
K Channels ◽  
Cranial Window ◽  
Calcitonin Gene ◽  
A Minor ◽  
Oxide Synthase ◽  
Camp Levels

Stimulation of adenylate cyclase appears to activate ATP-sensitive K+ channels in the basilar artery. We tested the hypothesis that calcitonin gene-related peptide (CGRP), which increases intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels, activates ATP-sensitive K+ channels and thereby causes vasodilatation. Using a cranial window in anesthetized rats, we examined responses of the basilar artery to CGRP in vivo. We also examined responses of the artery to another vasoactive peptide, vasoactive intestinal peptide (VIP). Topical application of CGRP (10(-11) to 10(-8) M) increased diameter of the basilar artery. Responses of the basilar artery to CGRP were almost abolished by a CGRP1 receptor antagonist, CGRP-(8-37). Vasodilatation in response to VIP was much smaller than that produced by CGRP. Dilator responses of the basilar artery to 10(-9) and 10(-8) M CGRP were inhibited by glibenclamide (10(-6) M), a selective inhibitor of ATP-sensitive K+ channels, by 69 +/- 19 and 41 +/- 9%, respectively. NG-nitro-L-arginine methyl ester (10(-5) M), an inhibitor of nitric oxide synthase, did not attenuate dilator response to 10(-8) M CGRP but inhibited responses to 10(-9) M CGRP by 34 +/- 12%. Indomethacin did not alter dilator responses to CGRP. These findings suggest that a minor component of CGRP-induced dilatation of the basilar artery is mediated by endothelium-derived relaxing factor. Vasodilatation in response to CGRP appears to be mediated primarily by direct activation of CGRP1 receptors on vascular muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of norepinephrine on rat basilar artery in vivo

1993 ◽  
Vol 264 (1) ◽  
pp. H178-H182 ◽  
Author(s):  
T. Kitazono ◽  
F. M. Faraci ◽  
D. D. Heistad
Keyword(s):  
Basilar Artery ◽  
Selective Inhibitor ◽  
K Channels ◽  
Cranial Window ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Oxide Synthase ◽  
Dependent Mechanism ◽  
Direct Activator

In anesthetized rats, we used a cranial window to examine effects of topical norepinephrine on diameter of the basilar artery in vivo. Topical application of norepinephrine increased the diameter of the basilar artery. NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, inhibited vasodilatation to acetylcholine but did not attenuate dilator responses to norepinephrine. Indomethacin also did not attenuate vasodilatation in response to norepinephrine. Dilatation of the basilar artery to norepinephrine was inhibited by propranolol and the beta 1-antagonist atenolol but not by the beta 2-antagonist butoxamine. Thus dilatation of the basilar artery in response to norepinephrine is produced by activation of beta 1-receptors and is not mediated by endothelium-derived relaxing factor or prostanoids. Glibenclamide, a selective inhibitor of ATP-sensitive K+ channels, partially inhibited vasodilatation in response to norepinephrine. Forskolin, a direct activator of adenylate cyclase, also increased the diameter of the basilar artery, and glibenclamide attenuated the dilatation. Thus dilatation of rat basilar artery in response to norepinephrine is mediated, in part, by activation of ATP-sensitive K+ channels, and activation of these K+ channels may be achieved by an adenosine 3',5'-cyclic monophosphate-dependent mechanism.

Effect of protein kinase C inhibitors on endothelin- and vasopressin-induced constriction of the rat basilar artery

1992 ◽  
Vol 263 (6) ◽  
pp. H1643-H1649 ◽  
Author(s):  
M. A. Murray ◽  
F. M. Faraci ◽  
D. D. Heistad
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Basilar Artery ◽  
Arginine Vasopressin ◽  
Vessel Diameter ◽  
Pkc Inhibitor ◽  
Cranial Window ◽  
Kinase C ◽  
Basilar Arteries

The goal of this study was to determine whether inhibitors of protein kinase C (PKC) attenuate constrictor responses of the basilar artery in vivo to endothelin and arginine vasopressin. In anesthetized rats, the diameter of basilar arteries was measured through a cranial window [control diameter 218 +/- 3 (SE) microns]. Vessel diameter was measured during topical application of agonists and antagonists. Sphingosine (10(-6) M), a PKC inhibitor that binds to the regulatory site of PKC, attenuated vasoconstriction in response to endothelin (10(-9), 10(-8), and 10(-7) M) and vasopressin (10(-9) and 10(-8) M). H-7 (10(-9) M), a PKC inhibitor that binds to the catalytic site of PKC, also inhibited vasoconstriction in response to endothelin and vasopressin. Sphingosine and H-7 did not affect baseline diameter and did not attenuate vasoconstriction in response to prostaglandin (PG) F2 alpha. The V1 antagonist [d(CH2)5Tyr(Me)]arginine vasopressin (10(-8) M) significantly inhibited constriction in response to vasopressin (10(-9) and 10(-8) M) but not PGF2 alpha (10(-6) M). These observations suggest that activation of PKC may contribute to endothelin-induced constriction of the basilar artery in vivo and that PKC may also be a mediator of V1-receptor-mediated constriction of the basilar artery in response to vasopressin.

scholarly journals Impact of Acute and Chronic Hypertension on Changes in Pial Collateral Tone In Vivo During Transient Ischemia

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 1019-1026
Author(s):  
Marilyn J. Cipolla ◽  
Siu-Lung Chan
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Chronic Hypertension ◽  
Spontaneously Hypertensive ◽  
Cranial Window ◽  
Pressor Therapy ◽  
Cerebral Artery Occlusion

We investigated vasoconstrictive responses of pial collaterals in vivo at baseline and during transient middle cerebral artery occlusion during chronic hypertension. A cranial window was used to measure diameter of leptomeningeal anastomoses (pial collaterals) in male Wistar (n=8) and spontaneously hypertensive rats (SHRs; n=8) using video dimensional analysis. Middle cerebral artery occlusion was induced by remote filament for 2 hours with 2 hours reperfusion. Phenylephrine was infused during ischemia as a pressor therapy. Active diameters of pial collaterals were significantly smaller in SHRs versus Wistar (14.1±1.5 versus 21.6±2.8 µm; P <0.01); however, passive diameters were similar (25.0±2.9 versus 25.0±2.6 µm; P >0.05). Basal tone of pial collaterals before occlusion was 42±5% in SHRs versus 15±4% in Wistar ( P <0.01). Tone decreased in both Wistar and SHRs during occlusion but remained higher in SHRs (9±2% versus 29±4%; P <0.05). Phenylephrine increased blood pressure in both groups but had little effect on leptomeningeal anastomoses diameters. Reperfusion caused vasoconstriction of pial collaterals, increasing tone from 8±1% to 20±5% in Wistar and 29±5% to 44±5% in SHRs ( P <0.01). Higher tone in pial collaterals from SHRs basally and during occlusion/reperfusion could limit flow to the penumbra and promote evolution of infarction. Sustained elevated tone of pial collaterals from SHRs with phenylephrine suggests pressor therapy may not be appropriate during chronic hypertension.

Impairment of endothelium-dependent dilatation of basilar artery during chronic hypertension

1990 ◽  
Vol 259 (5) ◽  
pp. H1455-H1462 ◽  
Author(s):  
W. G. Mayhan
Keyword(s):  
Nitric Oxide ◽  
Basilar Artery ◽  
Intravital Microscopy ◽  
Spontaneously Hypertensive Rats ◽  
Chronic Hypertension ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Baseline Diameter

The goal of this study was to determine whether responses of the basilar artery are altered during chronic hypertension. We measured the diameter of the basilar artery using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine (10 microM) dilated the basilar artery by 25 +/- 4% (means +/- SE) in WKY but by only 2 +/- 2% in SHR. Bradykinin (1.0 microM) dilated the basilar artery by 12 +/- 1% in WKY, but did not alter diameter in SHR (-0.1 +/- 2%). In contrast, nitroglycerin produced similar vasodilatation in WKY and SHR. Next, we examined the possibility that impaired vasodilatation in SHR may be related to the production of a cyclooxygenase constrictor substance. Indomethacin (10 mg/kg iv) did not restore vasodilatation in response to acetylcholine and bradykinin in SHR. Finally, we examined the role of nitric oxide in dilatation of the basilar artery in response to acetylcholine and bradykinin in WKY. NG-Monomethyl-L-arginine (L-NMMA; 1.0 microM) had little effect on baseline diameter but inhibited vasodilation in response to acetylcholine and bradykinin. Vasodilatation in response to nitroglycerin was not altered by L-NMMA. These findings suggest a profound impairment of endothelium-dependent dilatation of the basilar artery during chronic hypertension. In addition, impaired vasodilatation is not related to the production of a cyclooxygenase constrictor substance. Furthermore, dilatation of the basilar artery in WKY in response to acetylcholine and bradykinin appears to be related to the production of nitric oxide or a substance capable of liberating nitric oxide.

Intravital Studies on Cerebral Arteries in Hypertensive and Normotensive Rats

1982 ◽  
Vol 63 (s8) ◽  
pp. 81s-82s ◽  
Author(s):  
Barbro B. Johansson ◽  
Ludwig M. Auer ◽  
Ichiro Sayama
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Cerebral Arteries ◽  
Cortical Surface ◽  
Percentage Increase ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Cranial Window ◽  
Wky Rats ◽  
Wistar Kyoto

1. The diameters of main cortical surface branches of the middle cerebral artery were continuously monitored through a closed cranial window in spontaneously hypertensive rats (SHR) and in normotensive Wistar Kyoto (WKY) rats by aid of a multichannel video-angiometer under resting conditions and under maximal vasodilatation induced by hypercapnia. 2. Initial mean arterial pressure was 172 ± sem 9 mmHg in SHR and 103 ± 5 mmHg in WKY rats; during hypercapnia the corresponding values were 183 ± 9 and 127 ± 7 mmHg. 3. The resting diameter of the arteries was 55 ± 1 μm in SHR (n = 53) and 87 ± 1 μm in WKY rats (n = 53; P < 0.001). The percentage increase in diameter during vasodilatation (Paco2 70 mmHg) was larger in SHR (54%) than in WKY rats (36%). However, the maximum lumen diameter remained significantly smaller in SHR (84 ± 2 μm compared with 117 ± 5 μm in WKY rats; P < 0.001). No significant further dilatation was seen in either group after α-adrenoceptor blockade. 4. The smaller diameter of cortical arteries during vasodilatation is consistent with the concept that hypertensive vascular hypertrophy encroaches on the lumen in vivo. The larger percentage increase in diameter of cortical arteries in hypertensive rats corroborates Folkow's hypothesis on the haemodynamic consequences of an altered media/lumen ratio in hypertension. 5. There is no evidence that an enhanced sympatho-adrenergic tone prevents maximum vasodilatation during hypercapnia in SHR.

scholarly journals Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator of KCa2.x and KCa3.1 Channels

2019 ◽  
Vol 20 (17) ◽  
pp. 4118 ◽  
Author(s):  
Kloza ◽  
Baranowska-Kuczko ◽  
Toczek ◽  
Kusaczuk ◽  
Sadowska ◽  
...  
Keyword(s):  
Mesenteric Arteries ◽  
Spontaneously Hypertensive ◽  
Downstream Signaling ◽  
Calcium Activated Potassium Channels ◽  
Wistar Kyoto ◽  
Oxide Synthase ◽  
Prostacyclin Synthase ◽  
Promising Avenue

The aim of this study was to investigate the hemodynamic effects of SKA-31, an activator of the small (KCa2.x) and intermediate (KCa3.1) conductance calcium-activated potassium channels, and to evaluate its influence on endothelium-derived hyperpolarization (EDH)-KCa2.3/KCa3.1 type relaxation in isolated endothelium-intact small mesenteric arteries (sMAs) from spontaneously hypertensive rats (SHRs). Functional in vivo and in vitro experiments were performed on SHRs or their normotensive controls, Wistar-Kyoto rats (WKY). SKA-31 (1, 3 and 10 mg/kg) caused a brief decrease in blood pressure and bradycardia in both SHR and WKY rats. In phenylephrine-pre-constricted sMAs of SHRs, SKA-31 (0.01–10 µM)-mediated relaxation was reduced and SKA-31 potentiated acetylcholine-evoked endothelium-dependent relaxation. Endothelium denudation and inhibition of nitric oxide synthase (eNOS) and cyclooxygenase (COX) by the respective inhibitors l-NAME or indomethacin, attenuated SKA-31-mediated vasorelaxation. The inhibition of KCa3.1, KCa2.3, KIR and Na+/K+-ATPase by TRAM-34, UCL1684, Ba2+ and ouabain, respectively, reduced the potency and efficacy of the EDH-response evoked by SKA-31. The mRNA expression of eNOS, prostacyclin synthase, KCa2.3, KCa3.1 and KIR were decreased, while Na+/K+-ATPase expression was increased. Collectively, SKA-31 promoted hypotension and vasodilatation, potentiated agonist-stimulated vasodilation, and maintained KCa2.3/KCa3.1-EDH-response in sMAs of SHR with downstream signaling that involved KIR and Na+/K+-ATPase channels. In view of the importance of the dysfunction of endothelium-mediated vasodilatation in the mechanism of hypertension, application of activators of KCa2.3/KCa3.1 channels such as SKA-31 seem to be a promising avenue in pharmacotherapy of hypertension.

scholarly journals Attenuation and Recovery of Brain Stem Autoregulation in Spontaneously Hypertensive Rats

1998 ◽  
Vol 18 (3) ◽  
pp. 305-310 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Takanari Kitazono ◽  
Tetsuhiko Nagao ◽  
...  
Keyword(s):  
Brain Stem ◽  
Basilar Artery ◽  
Antihypertensive Treatment ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Doppler Flowmetry ◽  
Spontaneously Hypertensive ◽  
Large Arteries ◽  
Cranial Window ◽  
Severe Hypotension

Cerebral large arteries dilate actively around the lower limits of CBF autoregulation, mediated at least partly by nitric oxide, and maintain CBF during severe hypotension. We tested the hypothesis that this autoregulatory response of large arteries, as well as the response of arterioles, is altered in spontaneously hypertensive rats (SHR) and that the altered response reverts to normal during long-term antihypertensive treatment with cilazapril, an angiotensin-converting enzyme inhibitor. In anesthetized 6- to 7-month-old normotensive Wistar-Kyoto rats (WKY), 4- and 6- to 7-month-old SHR without antihypertensive treatment, and 6- to 7-month-old SHR treated with cilazapril for 10 weeks, local CBF to the brain stem was determined with laser—Doppler flowmetry and diameters of the basilar artery and its branches were measured through a cranial window during stepwise hemorrhagic hypotension. The lower limit of CBF autoregulation shifted upward in untreated SHR to 90 to 105 mm Hg from 30 to 45 mm Hg in WKY, and it reverted to 30 to 45 mm Hg in treated SHR. In response to severe hypotension, the basilar artery dilated by 21 ± 6% (mean ± SD) of the baseline internal diameter in WKY. The vasodilation was impaired in untreated SHR (10 ± 8% in 4-mo-old SHR and 4 ± 5% in 6- to 7-month-old SHR), and was restored to 22 ± 10% by treatment with cilazapril ( P < 0.005). Dilator responses of branch arterioles to hypotension showed similar attenuation and recovery as that of the basilar artery. The data indicate that chronic hypertension impairs the autoregulatory dilation of the basilar artery as well as branch arterioles and that antihypertensive treatment with cilazapril restores the diminished dilation toward normal.

Role of adenosine in noradrenergic neurotransmission in spontaneously hypertensive rats

1987 ◽  
Vol 253 (4) ◽  
pp. H909-H918 ◽  
Author(s):  
E. K. Jackson
Keyword(s):  
Plasma Levels ◽  
Spontaneously Hypertensive Rat ◽  
Base Line ◽  
Inhibitory Effects ◽  
Spontaneously Hypertensive ◽  
Vascular Responses ◽  
Rat Mesentery ◽  
Wistar Kyoto

The purpose of this study was to compare the in vivo role of adenosine as a modulator of noradrenergic neurotransmission in the spontaneously hypertensive rat (SHR) and Wistar-Kyoto control rat (WKY). In the in situ blood-perfused rat mesentery, vascular responses to periarterial (sympathetic) nerve stimulation (PNS) and to exogenous norepinephrine (NE) were enhanced in SHR compared with WKY. In both SHR and WKY, vascular responses to PNS were more sensitive to inhibition by adenosine than were responses to NE. At matched base-line vascular responses, compared with WKY, SHR were less sensitive to the inhibitory effects of adenosine on vascular responses to PNS, but SHR and WKY were equally sensitive with respect to adenosine-induced inhibition of responses to NE. Antagonism of adenosine receptors with 1,3-dipropyl-8-p-sulfophenylxanthine shifted the dose-response curve to exogenous adenosine sixfold to the right yet did not influence vascular responses to PNS or NE in either SHR or WKY. Furthermore, PNS did not alter either arterial or mesenteric venous plasma levels of adenosine in SHR or WKY, and plasma levels of adenosine in both strains were always lower than the calculated threshold level required to attenuate neurotransmission. It is concluded that in vivo 1) exogenous adenosine interferes with noradrenergic neurotransmission in both SHR and WKY; 2) SHR are less sensitive to the inhibitory effects of exogenous adenosine on noradrenergic neurotransmission than are WKY; 3) endogenous adenosine does not play a role in modulating neurotransmission in either strain under the conditions of this study; and 4) enhanced noradrenergic neurotransmission in the SHR is not due to defective modulation of neurotransmission by adenosine.

scholarly journals Duration of Electrically Induced Atrial Fibrillation Is Augmented by High Voltage of Stimulus with Higher Blood Pressure in Hypertensive Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Tomomi Nagayama ◽  
Yoshitaka Hirooka ◽  
Akiko Chishaki ◽  
Masao Takemoto ◽  
Yasushi Mukai ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Pressure ◽  
Arterial Pressure ◽  
High Voltage ◽  
Spontaneously Hypertensive Rats ◽  
Low Voltage ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High Stimulus ◽  
Wistar Kyoto

Objective.Many previous clinical studies have suggested that atrial fibrillation (AF) is closely associated with hypertension. However, the benefits of antihypertensive therapy on AF are still inconsistent, and it is necessary to explore the factors augmenting AF in hypertensive rats. The aim of the present study was to investigate the correlation between arterial pressure or voltage stimulus and to the duration of electrically induced AF in normotensive or hypertensive rats.Methods.AF was reproducibly induced by transesophageal atrial burst pacing in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). We did the burst pacing at high (20 V) or low (5 V) voltage.Results.Duration of AF did not correlate with systolic blood pressure (SBP) and stimulus voltage in WKY. However, only in SHR, duration of AF with high stimulus voltage significantly correlated with SBP and was significantly longer in high than in low voltage stimulus.Discussion and Conclusion.Duration of AF is augmented by high voltage stimulus with higher blood pressure in SHR.

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