Background and Purpose-The role of SK Ca and IK Ca channels in myogenic tone and endothelium-derived hyperpolarizing factor (EDHF) responsiveness was investigated under control conditions and after ischemia and reperfusion in parenchymal arterioles (PA) versus middle cerebral arteries (MCA). Methods-MCA and PA were dissected from male Wistar rats that were ischemic for 1 hour with 24 hours of reperfusion (nϭ12) or sham controls (nϭ12). Basal tone and reactivity to apamin (300 nmol/L), TRAM-34 (1.0 mol/L), and nitro-L-arginine (0.1 mmol/L) were compared in PA and MCA pressurized to 40 mm Hg and 75 mm Hg, respectively. SK Ca and IK Ca channel mRNA expression was measured using real-time PCR. Results-PA developed greater basal tone than MCA (42Ϯ4% versus 19Ϯ3%; PϽ0.01). Addition of apamin and TRAM-34 increased tone of PA by 25Ϯ3% and 16Ϯ2%, respectively, whereas MCA had no response to either inhibitor. After ischemia and reperfusion, the response to nitric oxide synthase inhibition (NOS) was diminished in PA, whereas EDHF responsiveness was preserved. In addition, stimulated EDHF dilation was partially reversed by apamin and completely reversed by TRAM-34 in both control and ischemic PA. SK Ca and IK Ca channel mRNA expression was similar in PA and MCA and not altered by ischemia and reperfusion. However, IK Ca channel mRNA expression was 4-to 5-fold greater than SK Ca channels. Conclusions-It appears that SK Ca and IK Ca channel activity diminishes basal tone of PA, but not MCA. The preservation of EDHF responsiveness of PA after ischemia and reperfusion suggests an important role for this vasodilator under conditions when NOS is inhibited.

Background and Purpose-Previous studies have shown that peroxisome proliferator-activated receptor ␥ (PPAR␥), a ligand-activated transcription factor expressed in vascular cells, is protective of the vasculature. We hypothesized that activation of PPAR␥ could prevent hypertensive remodeling of cerebral arteries and improve vascular function. Methods-Ten female Sprague-Dawley rats were treated with the nitric oxide synthase inhibitor N

Objective We investigated the effect of estrogen replacement on the structure and function of penetrating brain arterioles (PA) and blood-brain barrier (BBB) permeability. Methods Female ovariectomized Sprague Dawley rats were replaced with estradiol (E2) and estriol (E3) (OVX+E; N=13) and compared to ovariectomized animals without replacement (OVX; N=14) and intact controls (CTL, proestrous; N=13). Passive and active diameters, percent tone and passive distensibility of pressurized PA were compared. In addition, BBB permeability to Lucifer Yellow, a marker of transcellular transport, was compared in cerebral arteries. Results Ovariectomy increased myogenic tone in PA compared to CTL that was not ameliorated by estrogen treatment. Percent tone at 75 mmHg for CTL vs. OVX and OVX+E was 44 ± 3% vs. 51 ± 1% and 54 ± 3% (p<0.01 vs. CTL for both). No differences were found in passive diameters or distensibility between the groups. BBB permeability increased 500% in OVX vs. CTL animals, however, estrogen replacement restored barrier properties: flux of Lucifer Yellow for CTL, OVX and OVX+E was (ng/mL): 3.4 ± 1.2, 20.2 ± 5.3 (p<0.01 vs. CTL) and 6.15 ± 1.2 (n.s.). Conclusions These results suggest that estrogen replacement may not be beneficial for small vessel disease in the brain, but may limit BBB disruption and edema under conditions that cause it.

The effect of preexisiting hyperglycemia on cerebral blood flow (CBF) and brain penetrating arterioles before and after 2 h of ischemia and 30 min of reperfusion was determined. Male Wistar rats that were either hyperglycemic (50 mg/kg streptozotocin; n=24) or normoglycemic (n=24) were subjected to transient ischemia by filament occlusion or nonischemic. CBF was measured prior to ischemia using microspheres and during transient ischemia using laser Doppler. Edema was compared by wet/dry weights. Constriction to apamin, TRAM-34, and L-NNA, inhibitors of smalland intermediate-conductance calcium-activated potassium channels (SK and IK) and nitric oxide, were compared in penetrating arterioles from the ischemic hemisphere to investigate changes in basal tone and endothelium-dependent vasodilator responses. Preexisiting hyperglycemia did not affect CBF in non-ischemic animals or after transient ischemia; however, edema was significantly greater. Ischemia and reperfusion caused decreased basal tone in penetrating arterioles similarly in normoglycemic and hyperglycemic animals that was restored by apamin, and further increased by TRAM-34 and L-NNA. The restoration of tone in penetrating arterioles by apamin and TRAM-34 suggests that transient ischemia activates SK and IK channels in penetrating arterioles. This effect of ischemia was not different between normoglycemic and hyperglycemic animals, suggesting that it was related to ischemia and reperfusion rather than hyperglycemia.

Abstract-Previous studies have shown that pregnancy prevents hypertensive remodeling of cerebral arteries. In the present study, we sought to determine whether pregnancy could reverse preexisting remodeling. Nonpregnant virgin Sprague-Dawley rats were treated with the NO synthase inhibitor nitro-L-arginine (0.5 g/L in drinking water) for 2 weeks before mating, after which treatment continued until late gestation for a total of 5 weeks. Pregnant animals with preexisting hypertension (nϭ6) were compared with nonpregnant animals that were treated with nitro-L-arginine for either 2 (nϭ8) or 5 (nϭ9) weeks and compared with nontreated controls (nϭ8). Blood pressure, passive and active diameters, wall thickness, media thickness, and passive distensibility of cerebral arteries were compared between groups. Treatment with nitro-L-arginine caused a significant increase in mean arterial pressure in all of the groups compared with controls that was sustained for the entire study: 103Ϯ3 versus 137Ϯ2, 141Ϯ4, and 140Ϯ7 mm Hg (PϽ0.01). Both 2 and 5 weeks of hypertension caused inward eutrophic remodeling in nonpregnant animals, characterized by decreased inner and outer lumen diameters and no change in media thickness. Pregnancy reversed this remodeling, because late-pregnant animals with preexisting hypertension had inner and outer diameters similar to controls. Passive distensibility was significantly less, and active myogenic tone increased in all of the hypertensive animals, independent of pregnancy. These results demonstrate that pregnancy reverses preexisting hypertensive remodeling of cerebral arteries without a decrease in blood pressure. This reversal of protective remodeling during hypertension in pregnancy may be detrimental by lowering the upper limit of autoregulation, whereas blood pressure remains elevated. Key Words: hypertension pregnancy Ⅲ cerebral arteries Ⅲ remodeling C hronic hypertension is associated with significant remodeling and/or medial hypertrophy of cerebral arteries, which are thought to have a protective function. 1,2 Both remodeling and hypertrophy normalize wall stress that is elevated because of increased blood pressure and shift the autoregulatory curve to the higher range of pressures. 1-4 These processes are also protective of the microcirculation by attenuating increases in downstream pressure. For example, spontaneously hypertensive and stroke-prone spontaneously hypertensive rats, known to undergo medial hypertrophy, were less susceptible to bloodbrain barrier (BBB) disruption during acute hypertension than normotensive Wistar Kyoto rats that did not undergo medial hypertrophy. [5][6][7] In addition, medial hypertrophy is thought to stiffen the vascular wall, making cerebral arteries more resistant to forced dilatation during acute hypertension, thereby protecting the BBB from disruption. 1,2 Hypertension during pregnancy is one of the most common complications of pregnancy, occurring in Յ8% of all pregnancies. 8 It is a unique form of hypertension, somewhere between acute and chronic. I...