scholarly journals AT1 Receptors Prevent Salt-Induced Vascular Dysfunction in Isolated Middle Cerebral Arteries of 2 Kidney-1 Clip Hypertensive Rats

2013 ◽  
Vol 26 (12) ◽  
pp. 1398-1404 ◽  
Author(s):  
A. M. Beyer ◽  
K. Fredrich ◽  
J. H. Lombard
Keyword(s):  
Vascular Dysfunction ◽  
Cerebral Arteries ◽  
Hypertensive Rats ◽  
At1 Receptors ◽  
Middle Cerebral Arteries

scholarly journals Peroxynitrite Decomposition with FeTMPyP Improves Plasma-Induced Vascular Dysfunction and Infarction during Mild but not Severe Hyperglycemic Stroke

2012 ◽  
Vol 32 (6) ◽  
pp. 1035-1045 ◽  
Author(s):  
Sara Morales Palomares ◽  
Ira Gardner-Morse ◽  
Julie G Sweet ◽  
Marilyn J Cipolla
Keyword(s):  
Vascular Dysfunction ◽  
Cerebral Arteries ◽  
Stroke Outcome ◽  
Cerebrovascular Function ◽  
Middle Cerebral Arteries ◽  
Male Wistar Rats ◽  
Physiologic Saline ◽  
Severe Ischemia

We investigated mechanisms by which circulating factors during hyperglycemic (HG) stroke affect cerebrovascular function and the role of peroxynitrite in stroke outcome. Middle cerebral arteries (MCAs) were isolated from male Wistar rats and perfused with plasma from rats that were hyperglycemic for 5 to 6 days by streptozotocin and underwent either MCA occlusion (HG MCAO) or Sham surgery (HG Sham) compared with MCA perfused with physiologic saline (No plasma). Myogenic responses and endothelial function were compared in untreated MCA ( n=8/group) or with inhibitors of NADPH oxidase (apocynin; n=8), peroxynitrite (FeTMPyP; n=8) or endothelin-1 (ET-1)A (BQ-123; n=8). Finally, animals were treated in vivo before reperfusion after mild (<68% cerebral blood flow (CBF) decrease) or severe (>68% CBF decrease) MCAO with FeTMPyP ( n=12) or vehicle ( n=12) and CBF and infarction measured. The HG MCAO plasma increased tone in MCA versus No plasma ( P<0.05) that was reversed by FeTMPyP, but not by apocynin or BQ-123. The HG Sham plasma also increased tone in MCA ( P<0.05) that was reversed by BQ-123 only. In vivo, FeTMPyP was neuroprotective during mild, but not severe ischemia. These results show that circulating factors in plasma can affect cerebrovascular function through peroxynitrite generation and ET-1. In addition, peroxynitrite decomposition improves stroke outcome acutely during mild, but not severe HG ischemia.

scholarly journals Loss of cerebrovascular Shaker-type K+ channels: a shared vasodilator defect of genetic and renal hypertensive rats

2009 ◽  
Vol 297 (1) ◽  
pp. H293-H303 ◽  
Author(s):  
Ann A. Tobin ◽  
Biny K. Joseph ◽  
Hamood N. Al-Kindi ◽  
Sulayma Albarwani ◽  
Jane A. Madden ◽  
...  
Keyword(s):  
Cerebral Arteries ◽  
Chronic Hypertension ◽  
Mrna Levels ◽  
Hypertensive Rats ◽  
Western Blots ◽  
Spontaneously Hypertensive ◽  
Rat Models ◽  
Middle Cerebral Arteries ◽  
Wistar Kyoto ◽  
Renal Hypertensive Rats

The cerebral arteries of hypertensive rats are depolarized and highly myogenic, suggesting a loss of K+ channels in the vascular smooth muscle cells (VSMCs). The present study evaluated whether the dilator function of the prominent Shaker-type voltage-gated K+ (KV1) channels is attenuated in middle cerebral arteries from two rat models of hypertension. Block of KV1 channels by correolide (1 μmol/l) or psora-4 (100 nmol/l) reduced the resting diameter of pressurized (80 mmHg) cerebral arteries from normotensive rats by an average of 28 ± 3% or 26 ± 3%, respectively. In contrast, arteries from spontaneously hypertensive rats (SHR) and aortic-banded (Ao-B) rats with chronic hypertension showed enhanced Ca2+-dependent tone and failed to significantly constrict to correolide or psora-4, implying a loss of KV1 channel-mediated vasodilation. Patch-clamp studies in the VSMCs of SHR confirmed that the peak K+ current density attributed to KV1 channels averaged only 5.47 ± 1.03 pA/pF, compared with 9.58 ± 0.82 pA/pF in VSMCs of control Wistar-Kyoto rats. Subsequently, Western blots revealed a 49 ± 7% to 66 ± 7% loss of the pore-forming α1.2- and α1.5-subunits that compose KV1 channels in cerebral arteries of SHR and Ao-B rats compared with control animals. In each case, the deficiency of KV1 channels was associated with reduced mRNA levels encoding either or both α-subunits. Collectively, these findings demonstrate that a deficit of α1.2- and α1.5-subunits results in a reduced contribution of KV1 channels to the resting diameters of cerebral arteries from two rat models of hypertension that originate from different etiologies.

scholarly journals Introgression of Brown Norway CYP4A genes on to the Dahl salt-sensitive background restores vascular function in SS-5BN consomic rats

2012 ◽  
Vol 124 (5) ◽  
pp. 333-342 ◽  
Author(s):  
Kathleen M. Lukaszewicz ◽  
John R. Falck ◽  
Vijaya L. Manthati ◽  
Julian H. Lombard
Keyword(s):  
Vascular Function ◽  
Vascular Dysfunction ◽  
Cerebral Arteries ◽  
Dienoic Acid ◽  
Brown Norway ◽  
No Donor ◽  
Middle Cerebral Arteries ◽  
No Bioavailability ◽  
Relaxation Responses

The present study tested the hypothesis that the Dahl SS (salt-sensitive) rat has vascular dysfunction due, in part, to the up-regulation of the CYP4A/20-HETE (cytochrome P450 ω-hydroxylase 4A)/20-hydroxyeicosatetraenoic acid) system. To assess the role of vascular 20-HETE, SS rats were compared with SS-5BN consomic rats, carrying CYP4A alleles on chromosome 5 from the normotensive BN (Brown Norway) introgressed on to the SS genetic background. Cerebral arteries from SS-5BN rats had less CYP4A protein than arteries from SS rats fed either NS (normal-salt, 0.4% NaCl) or HS (high-salt, 4.0% NaCl) diet. ACh (acetylcholine)-induced dilation of MCAs (middle cerebral arteries) from SS and SS-5BN rats was present in SS-5BN rats fed on either an NS or HS diet, but absent in SS rats. In SS rats fed on either diet, ACh-induced dilation was restored by acute treatment with the CYP4A inhibitor DDMS (N-methyl-sulfonyl-12,12-dibromododec-11-enamide) or the 20-HETE antagonist 20-HEDE [20-hydroxyeicosa-6(Z),15(Z)-dienoic acid]. The restored response to ACh in DDMS-treated SS rats was inhibited by L-NAME (NGnitro-L-arginine methyl ester) and unaffected by indomethacin or MS-PPOH [N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide]. Vascular relaxation responses to the NO donor C5FeN6Na2O were intact in both SS and SS-5BN rats and unaffected by the acute addition of DDMS, indicating that the vascular dysfunction of the SS rat is due to a reduced bioavailability of NO instead of failure of the VSMCs (vascular smooth muscle cells) to respond to the vasodilator. Superoxide levels in cerebral arteries of SS-5BN rats [evaluated semi-quantitatively by DHE (dihydroethidium) fluorescence] were lower than those in the arteries of SS rats. These findings indicate that SS rats have an up-regulation of the CYP4A/20-HETE pathway resulting in elevated ROS (reactive oxygen species) and reduced NO bioavailability causing vascular dysfunction.

Electrical conduction within the cerebrovasculature of stroke-prone spontaneously hypertensive rats

1998 ◽  
Vol 76 (2) ◽  
pp. 194-201 ◽  
Author(s):  
John S Smeda ◽  
Shelley R King
Keyword(s):  
Electrical Conductivity ◽  
Membrane Potential ◽  
Gap Junction ◽  
Electrical Conduction ◽  
Cerebral Arteries ◽  
Sprague Dawley ◽  
Hypertensive Rats ◽  
Middle Cerebral Arteries ◽  
Length Constant ◽  
Electrotonic Potential

Alterations in electrical conductivity between smooth muscle cells (SMCs) can alter the spread and effectiveness of electromechanical SMC contraction. We attempted to determine whether alterations in pressure-dependent constriction (PDC) occurring in relation to stroke development within the middle cerebral arteries (MCAs) of Wistar-Kyoto stroke-prone hypertensive rats (SHRsp) were associated with changes in electrical conductivity between the SMCs. Current was injected into nonpressurized MCAs, using a suction electrode. The conducting distance along the length of the MCA where the amplitude of the membrane potential deflection (electrotonic potential) produced by current injection declined to 1/e (length constant) was used to measure conductivity. PDC to a 100 mmHg pressure step was measured with a pressure myograph. A loss of PDC in the MCAs of SHRsp preceded stroke development. Heptanol (4 mM), a gap junction communication inhibitor, reversibly inhibited conductivity and PDC in the MCA of prestroke SHRsp. The ability of heptanol to reversibly inhibit PDC was likely not related to it's ability to alter electrical conduction. The length constant of electrical conduction in the MCAs was about 0.75 mm and didn't differ between MCA sampled from pre- versus post-stroke SHRsp or Sprague-Dawley rats. It was concluded that alterations in electrical conductivity along the MCA could modify the spread of PDC, but such changes do not contribute to the loss of PDC within the MCA of poststroke SHRsp.Key words: membrane potential, electrotonic potential, middle cerebral arteries, myogenic response, gap junction, stroke-prone hypertensive rats.

Hypertension increases middle cerebral artery resting tone in spontaneously hypertensive rats: role of tonic vasoactive factor availability

2008 ◽  
Vol 114 (10) ◽  
pp. 651-659 ◽  
Author(s):  
José M. González ◽  
Beatriz Somoza ◽  
M. Victoria Conde ◽  
Maria S. Fernández-Alfonso ◽  
M. Carmen González ◽  
...  
Keyword(s):  
Cerebral Artery ◽  
Spontaneously Hypertensive Rats ◽  
Cerebral Arteries ◽  
Mesenteric Arteries ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Middle Cerebral Arteries ◽  
Myogenic Responses ◽  
Resting Tone

The present study explores the contribution of alterations in resting tone to cerebral artery narrowing in SHRs (spontaneously hypertensive rats) and the role of hypertension development. Young pre-hypertensive and adult fully hypertensive SHRs and age-matched Wistar–Kyoto rat controls were used. The contribution of basal vasoactive factors to resting tone was studied in middle cerebral arteries with pressure myography. Basal NO and O2− (superoxide anion) availability were determined with fluorescent indicators using confocal microscopy and lucigenin-enhanced chemiluminescence. Basal O2− was also assessed in mesenteric resistance arteries. Middle cerebral arteries from adult rats, but not young pre-hypertensive rats, had augmented myogenic responses and resting tone and decreased relaxation to sodium nitroprusside compared with their normotensive counterparts. Cerebral arteries from adult SHRs also had an increase in tonic NO associated with a decrease in basal O2− availability. Basal O2− was instead increased in mesenteric arteries from SHRs. The present results indicate that large cerebral arteries from SHRs have an increase in their resting tone as a consequence of sustained hypertension and that this is related to a decrease in NO responsiveness. We suggest that this increase in resting tone and myogenic responses could act as a protective mechanism against the development of stroke in SHRs. The present study also demonstrates some unusual findings regarding the current understanding of the NO/O2− balance in hypertension with important differences between vascular beds and draws attention to the complexity of this balance in cardiovascular health and disease.

Prevention of stroke and preservation of the functions of cerebral arteries by treatment with perindopril in stroke-prone spontaneously hypertensive rats

1998 ◽  
Vol 76 (1) ◽  
pp. 26-34 ◽  
Author(s):  
H Wang ◽  
J S Smeda ◽  
RMKW Lee
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Cerebral Arteries ◽  
Subsequent Development ◽  
Treatment Withdrawal ◽  
Prolonged Treatment ◽  
Control Group ◽  
Myogenic Response ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Middle Cerebral Arteries

The aim of this study was to determine whether the prevention of stroke with perindopril treatment in stroke-prone spontaneously hypertensive rats (SHRSP) is associated with the preservation of the myogenic properties of the cerebral arteries. After weaning at 4 weeks of age, male SHRSP were fed a Japanese-style rat diet with high salt to induce stroke development. Treatment with perindopril was given by gavage every morning beginning at 6 weeks of age. There were three experimental groups: two groups treated with 4 mg ·kg-1 ·day-1 perindopril for different durations (8 or 12 weeks) and one control group consisting of littermates given distilled water. All the control animals developed stroke and died within 14 weeks of age, and myogenic response of the middle cerebral arteries (MCA) to pressure increase was lost in these animals. In contrast, all the treated SHRSP survived during the treatment period, and myogenic response of the MCA was preserved. After withdrawal of the treatment, SHRSP treated for a longer period (12 weeks) also survived longer than those treated for a shorter period (8 weeks). The subsequent development of stroke and death following treatment withdrawal after 8 or 12 weeks of treatment was associated with the loss of pressure-dependent constriction in MCA. A longer treatment duration also increased the stiffness of the MCA. MCA from SHRSP after 12 weeks of treatment had smaller external and lumen diameters, and thicker walls than those from the 8-week treatment group. In a separate study, we found that treatment of SHRSP with 1 or 4 mg ·kg-1 ·day-1 of perindopril for 24 weeks beginning at 6 weeks of age also protected them against death related to stroke, because these rats survived up to 43 weeks of age, when the experiment was terminated. We conclude that there is an association between the absence of myogenic response in cerebral arteries and stroke development in SHRSP. Perindopril treatment preserves the myogenic response of MCA in SHRSP and prevents the stroke development in these animals. A prolonged treatment could increase the survival of SHRSP through a remodelling of the MCA and increasing the stiffness of the cerebral arteries.Key words: autoregulation, myogenic response, cerebral artery, stroke, perindopril, hypertension.

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