Search

Postural tachycardia syndrome (POTS), a chronic form of orthostatic intolerance, has signs and symptoms of lightheadedness, loss of vision, headache, fatigue, and neurocognitive deficits consistent with reductions in cerebrovascular perfusion. We hypothesized that young, normocapnic POTS patients exhibit abnormal cerebral autoregulation (CA) that results in decreased static and dynamic cerebral blood flow (CBF) autoregulation. All subjects had continuous recordings of mean arterial pressure (MAP) and CBF velocity (CBFV) using transcranial Doppler sonography in both the supine supine position and during a 70[degrees] head-up tilt. During tilt, POTS patients (n = 9) demonstrated a higher heart rate than controls (n = 7) (109 [+ or -] 6 vs. 80 [+ or -] 2 beats/min, P < 0.05), whereas controls demonstrated a higher MAP than POTS (87 [+ or -] 2 vs. 77 [+ or -] 3 mmHg, P < 0.05). Also during tilt, mean CBFV decreased 19.5 [+ or -] 2.6% in POTS patients versus 10.3 [+ or -] 2.0% in controls (P < 0.05). We then used a transfer function analysis of MAP and CFBV in the frequency domain to quantify these changes. The low-frequency (LF; 0.04-0.15 Hz) component of CBFV variability increased during tilt in POTS patients (supine: 3 [+ or -] 0.9 vs. tilt: 9 [+ or -] 2, P < 0.02). In POTS patients, there was an increase in LF and high-frequency coherence between MAP and CBFV, an increase in LF gain, and a lack of significant change in phase. Static CA may be less effective in POTS patients compared with controls, since immediately after tilt CBFV decreased more in POTS patients and was highly oscillatory and autoregulation did not restore CBFV to baseline values until the subjects became supine. Dynamic CA may be less effective in POTS patients because MAP and CBFV during tilt became almost perfectly synchronous. We conclude that dynamic and static autoregulation of CBF are less effective in POTS patients compared with control subjects during orthostatic challenge. chronic orthostasis; coherence; transcranial Doppler

Decreased cerebral blood flow (CBF) has been observed following the resuscitation from neonatal hypoxic-ischemic injury, but its mechanism is not known. We address the hypothesis that reduced CBF is due to a change in nitric oxide (NO) and superoxide anion [O.sup.-.sub.2] balance secondary to endothelial NO synthase (eNOS) uncoupling with vascular injury. Wistar rats (7 day old) were subjected to cerebral hypoxia-ischemia by unilateral carotid occlusion under isoflurane anesthesia followed by hypoxia with hyperoxic or normoxic resuscitation. Expired C[O.sub.2] was determined during the period of hyperoxic or normoxic resuscitation. Laser-Doppler flowmetry was used with isoflurane anesthesia to monitor CBF, and cerebral perivascular NO and [O.sup.-.sub.2] were determined using fluorescent dyes with fluorescence microscopy. The effect of tetrahydrobiopterin supplementation on each of these measurements and the effect of apocynin and [N.sup.[omega]]-nitro-L-arginine methyl ester (L-NAME) administration on NO and 02 were determined. As a result, CBF in the ischemic cortex declined following the onset of resuscitation with 100% [O.sub.2] (hyperoxic resuscitation) but not room air (normoxic resuscitation). Expired C[O.sub.2] was decreased at the onset of resuscitation, but recovery was the same in normoxic and hyperoxic resuscitated groups. Perivascular NO-induced fluorescence intensity declined, and [O.sup.-.sub.2]-induced fluorescence increased in the ischemic cortex after hyperoxic resuscitation up to 24 h postischemia. L-NAME treatment reduced 02 relative to the nonischemic cortex. Apocynin treatment increased NO and reduced [O.sup.-.sub.2] relative to the nonischemic cortex. The administration of tetrahydrobiopterin following the injury increased perivascular NO, reduced perivascular [O.sup.-.sub.2], and increased CBF during hyperoxic resuscitation. These results demonstrate that reduced CBF follows hyperoxic resuscitation but not normoxic resuscitation after neonatal hypoxic-ischemic injury, accompanied by a reduction in perivascular production of NO and an increase in [O.sub.2]. The finding that tetrahydrobiopterin, apocynin, and L-NAME normalized radical production suggests that the uncoupling of perivascular NOS, probably eNOS, due to acquired relative tetrahydrobiopterin deficiency occurs after neonatal hypoxic-ischemic brain injury. It appears that both NOS uncoupling and the activation of NADPH oxidase participate in the changes of reactive oxygen concentrations seen in cerebral hypoxic-ischemic injury. apocynin; neonatal rat; vasculature; [N.sup.[omega]]-nitro-L-arginine methyl ester

We hypothesize that cerebral ischemia leads to enhanced expression of endothelin (ET), 5-hydroxytryptamine (5-HT), and angiotensin II (ANG II) receptors in the vascular smooth muscle cells. Our aim is to correlate the upregulation of cerebrovascular receptors and the underlying molecular mechanisms with the reduction in regional and global cerebral blood flow (CBF) after subarachnoid hemorrhage (SAH). SAH was induced by injecting 250 [micro]l blood into the prechiasmatic cistern in rats. The cerebral arteries were removed 0, 1, 3, 6, 12, 24, and 48 h after the SAH for functional and molecular studies. The contractile responses to ET-1. 5-carboxamidotryptamine (5-CT), and ANG II were investigated with myograph. The receptor mRNA and protein levels were analyzed by quantitative real-lime PCR and immunohistochemistry, respectively. In addition, regional and global CBFs were measured by an autoradiographic method. As a result, SAH resulted in enhanced contractions to ET-1 and 5-CT. ANG II [via ANG II type 1 ([AT.sub.1]) receptors] induced increased contractile responses [in the presence of the ANG II type 2 ([AT.sub.2]) receptor antagonist PD-123319]. In parallel the [ET.sub.B], [5-HT.sub.1B], and [AT.sub.1] receptor, mRNA and protein levels were elevated by time. The regional and global CBF showed a successive reduction with time after SAH. In conclusion, the results demonstrate for the first time that SAH induces the upregulation of [ET.sub.B], [5-HT.sub.1B], and [AT.sub.1] receptors in a time-dependent manner both at functional, mRNA, and protein levels. These changes occur in parallel with a successive decrease in CBF. Thus there is a temporal correlation between the changes in receptor expression and CBF reduction, suggesting a linkage. cerebral blood flow; cerebral ischemia

Estrogen appears to enhance cerebral blood flow (CBF). An association between CBF and physiologically altered hormonal levels due to menstrual cycle, menopause, or exogenous manipulations such as ovariectomy or hormone replacement therapy has been demonstrated. The purpose of this study was to determine the association between ovarian stimulation and CBF in vivo by measuring blood flow in the internal carotid artery (ICA) after pituitary suppression and during controlled ovarian stimulation in women undergoing in vitro fertilization treatment cycles. ICA volume flows were measured by angle-independent dual-beam ultrasound Doppler in 12 women undergoing controlled ovarian stimulation. Measurements were performed after pituitary/ovarian suppression, in the late follicular phase, and at midluteal phase. Blood flow in the ICA increased by 22.2% and 32% in the late follicular and midluteal phases compared with the respective values obtained during ovarian suppression (P < 0.0005 and P < 0.0001, respectively). There was a significant correlation between increments in estrogen levels and increments in CBF when the late follicular phase was compared with the ovarian suppression period (r = 0.8, P < 0,001). Mean blood flow velocity significantly increased (by 15.7% and 16.9%, respectively) and cerebral vascular resistance significantly decreased (by 17.6% and 26.5%) during the late follicular and midluteal phases compared with respective measures during ovarian suppression. There was a significant correlation between an increase in estrogen levels and a decrease in cerebral vascular resistance when the late follicular phase was compared with the ovarian suppression period (r = -0.6, P < 0.05). These changes imply sex hormone-associated intracranial vasodilation leading to increased CBF during controlled ovarian stimulation. estrogen; progesterone; angle-independent Doppler; in vitro fertilization

The purpose of this study was to characterize vascular responses and to examine mechanisms of vascular dysfunction in TallyHo mice, a new polygenic model of Type II diabetes. Responses of cerebral arterioles and carotid arteries were examined in vivo by using a cranial window and in vitro by using tissue baths, respectively. Dilatation of cerebral arterioles (baseline diameter = 33 [+ or -] [micro]m) in response to acetylcholine, but not to nitroprusside, was markedly reduced (P < 0.05) in TallyHo mice. Responses of cerebral arterioles to acetylcholine in TallyHo mice were restored to normal with polyethylene glycol-superoxide dismutase (100 U/ml; a superoxide scavenger). Responses to acetylcholine were also greatly impaired (P < 0.05) in the carotid arteries from TallyHo mice. Phenylephrine- and serotonin-, but not to KCl- or U46619-, induced contraction was increased two- to fourfold (P < 0.05) in carotid arteries of TallyHo mice. Responses to phenylephrine and serotonin were reduced to similar levels in the presence of Y-27632 (an inhibitor of Rho kinase; 3 [micro]mo1/1). These findings provide the first evidence that vascular dysfunction is present in TallyHo mice and that oxidative stress and enhanced activity of Rho kinase may contribute to altered vascular function in this genetic model of Type II diabetes. carotid artery; cerebral circulation; endothelium; microcirculation