Changes In Mean Arterial Blood Pressure Research Articles

Simvastatin Reduces Pressor Response to Centrally Administered Angiotensin II

Angiotensin II (Ang II) plays a pivotal role in regulation of the circulatory system. Activation of angiotensin type 1 (AT1) receptors in several brain regions leads to an increase in blood pressure. Accumulating data suggest that statins affect the peripheral action of Ang II; however, their central effects are poorly recognized. The study was aimed to determine whether simvastatin interferes with the brain angiotensin system in rats. Twelve-week-old, Sprague-Dawley rats were divided into two groups. Untreated group was maintained on tap water, whereas simvastatin group received water containing simvastatin for the following 12 weeks. Later, both groups were subjected to experiments in which mean arterial blood pressure (MABP) and heart rate (HR) were recorded during baseline conditions and after intracerebroventricular (ICV) infusion of either saline, Ang II, or losartan. ICV infusion of Ang II elicited a significant increase in MABP in both groups. However, the pressor response in the simvastatin group was significantly smaller than that in the untreated group. There was no significant change in MABP after ICV infusion of saline or losartan. ICV infusion of Ang II elicited a significant increase in HR in the untreated group but not in the simvastatin group. There was no significant change in HR after ICV infusion of saline or losartan. The results show that simvastatin reduces the pressor response to ICV-infused Ang II in rats. This implies that statins may affect the central regulation of the circulatory system, especially when the brain angiotensin system is stimulated.

Muscle Sympathetic Nerve Activity Responses To Plantar Flexion In Humans

Previous studies examining muscle sympathetic nerve activity (MSNA) responses to exercise have focused on arm exercise with only limited data examining responses to leg exercise. PURPOSE: To examine MSNA responses to plantar flexion from one leg. The uniqueness of this experimental paradigm is that plantar flexion engages the gastrocnemius and soleus muscles, which are the major muscles that are activated during running. We hypothesized that MSNA would increase during fatiguing exercise. METHODS: Eleven healthy subjects (27 ± 1 yr) performed a graded bout of plantar flexion to fatigue followed by postexercise muscle ischemia (PEMI). Because time to fatigue varied between subjects, data were expressed as a percent of time to fatigue. MSNA, heart rate, and arterial blood pressure were measured continuously throughout the protocol. RESULTS: Heart rate and arterial blood pressure increased as a function of work rate. Maximal heart rate and mean arterial blood pressure changes were Δ25 ± 2 beats/min and Δ17 ± 3 mmHg, respectively (P<0.001). MSNA was significantly increased only after 50% time to fatigue. MSNA increased from 9 ± 2 bursts/min at rest to 14 ± 2 and 18 ± 2 bursts/min at 75% of fatigue and fatigue, respectively (P<0.001). During PEMI heart rate returned back to baseline, but was still significantly increased above baseline (Δ8 ± 1 beats/min). Mean arterial blood pressure was significantly reduced from pressures at fatigue, but remained elevated from baseline (Δ9 ± 2 mmHg). MSNA remained elevated during PEMI (18 ± 2 bursts/min). CONCLUSION: Plantar flexion elicits significant neurocardiovascular responses that appear to be primarily mediated by the muscle metaboreflex. The current experimental paradigm provides an effective exercise model to examine leg muscle reflexes in humans. Supported by the National Institutes of Health P01-HL-077670.

약용식물 추출물이 흰쥐의 뇌혈류학적 변화에 미치는 영향

As an attempt to develop new functional health beverage by using medicinal herb, we investigated the effect of medicinal plant extract (MPE) on mean arterial blood pressure (MABP) and regional cerebral blood flow (rCBF) of rats. The changes of MABP and rCBF were determined by LDF methods. LDF allows for real time, noninvasive, continuous recordings of local CBF. MABP in MPE treated rats showed significant change of MPE 1.0 and 10.0 mg/kg. MPE i.v. administration showed significant increase of rCBF in a dose-dependent manner. Propranolol pretreated MABP showed significant change in the increase of MPE. rCBF of propranolol pretreated rats showed significant change from the i.v. injection concentration of 1.0 and 10.0 mg/kg. The ischemia/ reperfusion induced oxidative stress may have contributed to cerebral damage in rats, and the present study provides clear evidence for the beneficial effect of MPE on ischemia induced brain injury. Also, the action mechanism in elevation effect of MPE on rCBF might be concerned with the role of β-adrenoceptor. The exact component and mechanism remains for the future study.

Heart rate and blood pressure effects during caloric vestibular testing

To determine whether the caloric vestibular test causes significant changes in heart rate and mean arterial blood pressure. Changes in heart rate and mean arterial blood pressure before and after caloric irrigation were compared with the degree of nystagmus (as measured by maximum slow phase velocity) and the patient's subjective dizziness (scored from 0 to 10). A cardiologist reviewed each patient's heart rate and mean arterial blood pressure changes. Patients' anxiety levels were also assessed. Eighteen patients were recruited. There were no adverse events in any patient. There were no overall significant differences between the heart rate and mean arterial pressure before and after each irrigation. There was a significant correlation between the maximum slow phase velocity and patients' subjective dizziness scores. Heart rate and mean arterial blood pressure are not significantly influenced by the caloric vestibular test. This preliminary study will enable patients with stable cardiovascular disease to be recruited for further risk determination.

Impairment of baroreflex control of heart rate and structural changes of cardiac ganglia in conscious streptozotocin (STZ)-induced diabetic mice

Baroreflex control of heart rate (HR) is impaired in human diabetes mellitus and in large experimental models. However, baroreflex impairment in diabetic mouse models and diabetes-induced remodeling of baroreflex circuitry are not well studied. We examined the impairment of baroreflex control of heart rate (HR) and assessed structural remodeling of cardiac ganglia in the streptozotocin (STZ)-induced diabetic mouse model. FVB mice were either injected with vehicle or STZ. Group 1: mice were anesthetized and the femoral artery and vein were catheterized at the 30th day after vehicle or STZ injection. On the second day after surgery, baroreflex-mediated HR responses to sodium nitroprusside (SNP) and phenylephrine (PE)-induced mean arterial blood pressure (MABP) changes were measured in conscious mice. Group 2: Fluoro-Gold was administered (i.p.) to label cardiac ganglia in each mouse at the 25th day after vehicle or STZ injection. After another five days, animals were perfused and cardiac ganglia were examined using confocal microscopy. Compared with control, we found in STZ mice: 1) the HR decreased, but MABP did not. 2) The PE-induced increases of MABP were decreased. 3) Baroreflex bradycardia was attenuated in the rapid MABP ascending phase but the steady-state ΔHR/ΔMABP was not different at all PE doses. 4) SNP-induced MABP decreases were not different. 5) Baroreflex tachycardia was attenuated. 6) The sizes of cardiac ganglia and ganglionic principal neurons were decreased. 7) The ratio of nucleus/cell body of cardiac ganglionic neurons was increased. We conclude that baroreflex control of HR is impaired in conscious STZ mice. In addition, diabetes may induce a significant structural remodeling of cardiac ganglia. Such an anatomical change of cardiac ganglia may provide new information for the understanding of diabetes-induced remodeling of the multiple components within the baroreflex circuitry.

Comparison of two regimes of thiopental and propofol for I-gel supraglottic airway device insertion.

Background:The I-gel mask is a novel supraglottic airway device. The objective of this study is to compare the insertion conditions for I-gel, using thiopental in two dosage regimes and propofol.Materials and Methods:A prospective, randomized, double-blind design was used. Ninety patients included in the study were classified at induction into group I that received intravenous 2.5 mg.Kg-1 propofol, group II that received 6 mg.Kg-1 thiopental and group III that received 7 mg.Kg-1 thiopental. Mean arterial blood pressure (MABP) and heart rate (HR) were recorded immediately before, after insertion and 5 minutes later, as well as the baseline hemodynamic variables. Tolerance of I-gel insertion was assessed using a scoring system.Results:Insertion conditions for I-gel supraglottic airway device showed significantly higher incidence of jaw relaxation (P=0.0008, 0.02 in groups I and III, respectively). No significant difference was found in the incidence of breath holding, lacrimation and stridor between the groups (P>0.05). The incidence of coughing/movement was significantly less in groups I and III (P=0.012, 0.04, respectively). Insertion time was significantly less in groups I and III (P<0.0001). The changes in MABP and HR were significantly less in groups I and III (P<0.0001).Conclusion:The use of thiopental at a dose of 7 mg.Kg-1 as an induction agent produced comparable I-gel supraglottic airway device insertion conditions with 2.5 mg.Kg-1 propofol in comparison to thiopental at 6 mg.Kg.-1.

Phosphorylation of spinal signaling-regulated kinases by acute uterine cervical distension in rats

Background Spinal extracellular signaling-regulated kinase 1 and 2 (ERK 1/2) have been found to contribute to nociceptive processing, but the role of spinal ERK 1/2 in visceral pain related to the uterine cervix, the source of pain during the first stage of labor, is unknown. The aim of this study was to investigate ERK activation (phosphorylation) in spinal dorsal horn neurons after acute uterine cervical distension. Methods Under intraperitoneal anesthesia using chloral hydrate 300 mg/kg, female Sprague-Dawley rats were exposed to a 10-s uterine cervical distension of 25, 50, 75, and 100 g or no distension (sham). The electromyographic response in the rectus abdominis muscle and mean arterial blood pressure and heart rate changes to uterine cervical distension were determined. The numbers of phosphorylated-ERK 1/2- immunoreactive (pERK 1/2-IR) dorsal horn neurons in cervical (C5-8), thoracic (T5-8), thoracolumbar (T12-L2) and lumbosacral (L 6-S 1) segments were counted using immunohistochemistry. Results Compared with the non-distended sham rats, uterine cervical distension resulted in a stimulus-dependent increase in electromyographic activity and the number of pERK-IR neurons that selectively located to the thoracolumbar segment, mostly in the deep dorsal and the central canal regions. The time course study demonstrated that spinal ERK activation peaked at 60 min with a slow decline for 120 min after uterine cervical distension stimulation. Conclusion This study suggests that activation of spinal ERK might be involved in acute visceral pain arising from the uterine cervix.

Intolerance to initial orthostasis relates to systolic BP changes in elders

To explore the association of early symptoms of orthostatic intolerance (OI) with systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressure changes in a sample of community-dwelling older people undergoing an active stand test; and to establish whether SBP and DBP changes have different symptomatic correlates during early orthostasis. A total of 224 community-dwelling older subjects (mean age 72.6 years, 68.8% females) were included. All had a Mini-Mental State Examination score >or=23 and no risk factors for autonomic neuropathy. Subjects were monitored with the Finometer Pro device. Variables reflecting blood pressure changes (absolute low: nadir, magnitude of drop: delta, and speed of recovery) were extracted for SBP, DBP and MAP with the BeatScope software (5-s averages method), and correlated with self-reported OI during active stand. Of the 224 subjects, 62 (27.7%) reported OI. SBP changes had strong bivariate associations with OI, but not DBP changes. A logistic regression model suggested that the rate of recovery of SBP during the first 30 s following active stand is more important as a determinant of OI than SBP nadir or delta. Subjects who recovered at least 80% of their baseline SBP within 30 s post-stand were very unlikely to report OI. Our study suggests that orthostatic SBP changes may be more important than DBP changes as determinants of early OI during active stand. The crucial importance of the quick recovery of SBP in order to avoid OI is biologically plausible and is discussed in the context of initial OH pathophysiology.

The Sit-to-Stand Technique for the Measurement of Dynamic Cerebral Autoregulation

Measurement of cerebral autoregulation is important for the evaluation and management of a number of clinical disorders that affect cerebral blood flow. We currently lack simple bedside measures that mimic common physiologic stresses. Therefore, we evaluated a new sit-to-stand technique as an alternative method to the frequently-used thigh-cuff technique in healthy volunteers. Continuous middle cerebral artery (MCA) blood flow velocities (BFV) and arterial blood pressure (ABP) were measured in response to standing from a sitting position, or rapid thigh-cuff deflation in 24 healthy subjects (50 ± 22 y). Autoregulatory index (ARI) was calculated as the BFV response for step changes in ABP using a second-order differential equation with a set of parameters that can be used to grade the performance of autoregulation. Of these 24 subjects, 30% could tolerate only two thigh-cuffs and refused to proceed with the third cuff, whereas none of our subjects had any difficulty with performing the three sit-to-stand trials. The two techniques produced similar changes in mean ABP, but the times to nadir of the blood pressure and BFV were significantly faster for the thigh-cuff. The mean group ARIs were similar between the two techniques. Although between-subjects variability was higher for sit-to-stand ARIs, the within-subject sit-to-stand ARI variability was small. Thus, for the assessment of cerebral autoregulation, the sit-to-stand procedure is well tolerated and produces ARI values that have low within-subject variability. The sit-to-stand technique appears to be a suitable measure of individual ARI values for inferring dynamic cerebral autoregulation. E-mail: fsorond@partners.org

Exogenous hydrogen sulfide produces hemodynamic effects by triggering central neuroregulatory mechanisms.

Recently, it was found that hydrogen sulfide (H2S) may serve as an important transmitter in peripheral organs as well as in the brain. The aim of the present study was to evaluate the possible function of H2S in the brain regulation of the circulatory system. Experiments were performed on conscious, male, Wistar-Kyoto rats. Mean arterial blood pressure (MABP) and heart rate (HR) were recorded continuously under baseline conditions and during infusions into the lateral cerebral ventricle (LCV) of the experimental animals. In control series LCV infusion of vehicle (Krebs-Henseleit bicarbonate-buffer) did not cause significant changes in MABP or HR. LCV infusion of H2S donor (NaHS) at the rate of 400 n/h resulted in an increase in MABP, whereas infusions at the rate of 100 n/h and 200 n/h failed to change MABP. On the other hand LCV infusion of H2S donor at the rate of 200 n/h caused a significant increase in HR while infusion at the rate of 400 n/h produced an increase in HR, which was smaller than this observed during infusion at the rate of 200 n/h. H2S donor administered at the rate of 100 n/h failed to affect HR. In conclusion, the present study demonstrates that exogenous hydrogen sulfide changes hemodynamic parameters by centrally mediated mechanisms. The hemodynamic effect seems to be dependent on H2S concentration in cerebrospinal fluid. It appears that the hypertensive response may occur at a concentration, which does not exceed twice the physiological level.

Cerebral Blood Flow Response in Adenosine 2a Receptor Knockout Mice during Transient Hypoxic Hypoxia

We evaluated cerebral blood flow by laser Doppler during 30 secs of hypoxia (0.10 FiO(2)) in anesthetized, ventilated adenosine 2a receptor knockout (A2aR KO) and wild-type (WT) mice to test the hypothesis that cerebral hypoxic hyperemia in KO mice would be attenuated. We also studied the effects of selective and nonselective A2aR antagonists. During 30 secs of hypoxia, P(a)O(2) decreased significantly (P<0.05) and to a similar degree in both types of mice, whereas P(a)CO(2) remained relatively stable. However, mean arterial blood pressure (MABP) decreased to a greater extent (P<0.05) during hypoxia in KO mice (58.6+/-1.5 mm Hg) than in WT animals (76.1+/-3.2 mm Hg). Consequently, in a separate group of mice, we stabilized and matched MABP during hypoxia. Hypoxic hyperemia was attenuated by 38% (P<0.05) in KO animals whose MABP was uncontrolled, and by 81% (P<0.05) in KO animals whose MABP changes were matched to the MABP in the hypoxic WT mice. In animals treated with adenosine antagonists, hypoxic hyperemia was decreased by 44% to 48% (P<0.05) in WT mice, but was without effect in KO mice. We conclude that adenosine via A2aR is responsible for a significant proportion of the hyperemia during hypoxia.

High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage

Because oral calcium channel blockers appear to reduce the severity of cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), interest in their application intraarterially has emerged for cases in which noninvasive means of alleviating vasospasm are unsuccessful. Studies to date have been limited to the administration of low intraarterial doses because of concerns about hemodynamic stability and changes in intracranial pressure. These doses, although effective in cases of milder vasospasm, were inadequate in severe cases. The authors present a series of 10 patients with cerebral vasospasm who underwent 12 procedures in which they received > or = 20 mg of intraarterial verapamil per procedure. A retrospective review was undertaken of all patients who underwent endovascular treatment for cerebral vasospasm due to aneurysmal SAH by the senior author between February 2005 and October 2006. Ten patients were identified who had undergone a total of 12 procedures during which > or =20 mg of intraarterial verapamil had been administered. From angiography reports, anesthesia records, and nursing records, we obtained pre- and postverapamil mean arterial blood pressures (MABPs), heart rates, intracranial pressures (ICPs) (when available), and visible changes in the degree of vasospasm. No statistically significant changes in MABP, heart rate, or ICP were observed after administration of > or = 20 mg of intraarterial verapamil, and the degree of improvement in vasospasm was statistically significant based on our grading system. No correlation was found between the change in hemodynamic parameters and the total dose of verapamil. This study indicates that high-dose intraarterial verapamil may be used to treat cerebral vasospasm without compromising hemodynamic stability or increasing ICP.

Renal denervation eliminates the natriuretic effect of isotensive sodium loading in conscious rats

It was hypothesized that the renal nerve activity (RNA) mediates the natriuretic response to an infusion of NaCl, which does not change mean arterial blood pressure (MABP). This was tested in trained rats supplied with appropriate chronic instrumentation. NaCl solution (1 M) was infused i.v. at 0.02 ml/min/kg (4–5 μl/min) for 2 h during measurements of circulatory, endocrine, and renal variables including RNA. During NaCl infusion RNA decreased by 15% (p&lt;0.05) within 30 min of infusion and reached a nadir of −25% (p&lt;0.05). Renal denervation per se decreased MABP by 15.5 mmHg (p&lt;0.01). In sham operated rats, NaCl infusion increased plasma Na+ by 1.6 mmol/l (repeated measures ANOVA, p&lt;0.03) but left MABP unchanged while heart rate (HR) decreased (455±7 to 427±7 bpm, p&lt;0.0001). Urine flow tended to increase (p=0.056); sodium excretion increased 4‐fold (1.4±0.2 to 6.0±0.6 μmol/min, p&lt;0.0001) while potassium excretion remained stable (2.2±0.3 to 2.3±0.4 μmol/min). NaCl infusion to renally denervated rats decreased HR similarly (423±17 to 393±20 bpm, p&lt;0.005). In contrast, however, sodium excretion remained constant (2.2±0.8 to 3.9±0.9, p=0.68) despite a significant increase in MABP (102±3 to 109±3 mmHg, p&lt;0.0001). It is concluded that a physiological sodium load increases sodium excretion by mechanisms dependent on renal nerves.Supported by the Danish Medical Research Council and the Novo Nordisk Foundation.

Impaired Autoregulation in Preterm Infants Identified by Using Spatially Resolved Spectroscopy

The absence of cerebral autoregulation in preterm infants has been associated with adverse outcome, but its bedside assessment in the immature brain is problematic. We used spatially resolved spectroscopy to continuously measure cerebral oxygen saturation (expressed as a tissue-oxygenation index) and used the correlation of tissue-oxygenation index with spontaneous fluctuations in mean arterial blood pressure to assess cerebral autoregulation. The tissue-oxygenation index and mean arterial blood pressure were continuously measured in very premature infants (n = 24) of mean (+/-SD) gestational age of 26 (+/-2.3) weeks at a mean postnatal age of 28 (+/-22) hours. The correlation between mean arterial blood pressure and tissue-oxygenation index in the frequency domain was assessed by using cross-spectral analysis techniques (coherence and transfer-function gain). Values of coherence reflect the strength of linear correlation, whereas transfer-function gain reflects the amplitude of tissue-oxygenation index changes relative to mean arterial blood pressure changes. High coherence (coherence > or = 0.5) values were found in 9 infants who were of lower gestational age, lower birth weight, and lower mean arterial blood pressure than infants with coherence of < 0.5; high-coherence infants also had higher median Clinical Risk Index for Babies scores and a higher rate of neonatal deaths. Coherence of > or = 0.5 predicted mortality with a positive predictive value of 67% and negative predictive value of 100%. In multifactorial analysis, coherence alone was the best predictor of mortality and Clinical Risk Index for Babies score alone was the best predictor of coherence. High coherence between mean arterial blood pressure and tissue-oxygenation index indicates impaired cerebral autoregulation in clinically sick preterm infants and is strongly associated with subsequent mortality. Cross-spectral analysis of mean arterial blood pressure and tissue-oxygenation index has the potential to provide continuous bedside assessment of cerebral autoregulation and to guide therapeutic interventions.

Functional Changes in Baroreceptor Afferent, Central, and Efferent Components of the Baroreflex Circuitry in Type 1 Diabetic Mice (OVE26)

Baroreflex control of heart rate (HR) is impaired in diabetes mellitus. We hypothesized that diabetes induced functional changes of the neural components at multiple sites within the baroreflex arc. OVE26 diabetic and FVB control mice were anesthetized. Baroreflex‐mediated HR responses to sodium nitroprusside (SNP)‐ and phenylephrine (PE)‐induced mean arterial blood pressure (MAP) changes were measured. Baroreceptor afferent function was characterized by measuring the percent change of the baseline of integrated aortic depressor nerve activity (Int ADNA) in response to MAP changes. The HR responses to electrical stimulation of the left aortic depressor nerve and the right vagus nerve were assessed. Compared to FVB control mice, we found in OVE26 mice that (1) Reflex‐mediated bradycardia and tachycardia were reduced (p&lt;0.05). (2) The baroreceptor afferent function in response to MAP increase did not differ (p&gt;0.05), as assessed by the parameters of the logistic function curve. But, the inhibition of Int ADNA in response to MAP decrease was attenuated (p&lt;0.05). (3) The maximum amplitude of HR responses to right vagal efferent stimulation was augmented (P&lt;0.05). (4) The maximum amplitude of HR responses to left ADN stimulation was decreased (p&lt;0.05). We conclude that a selective deficit of central mediation of reflex bradycardia contributes to the overall attenuation of baroreflex control of HR in OVE26 mice.

Manual Assessment of the Initial Fall in Blood Pressure After Orthostatic Challenge at High Altitude

Dizziness is a symptom of acute mountain sickness (AMS). This study tested whether immediate fall in systolic blood pressure (BP) on standing was more severe at altitude and whether this was associated with symptoms of dizziness. Eighty-five lowlanders flew into La Paz, Bolivia (3650 m), and after 4 to 5 days of acclimatization ascended in 90 minutes to the Chacaltaya Laboratory (5200 m) by road. Blood pressure was measured on 5 occasions, 3 times at 5200 m and twice at sea level, before and after the expedition using a mercury sphygmomanometer. Both a supine and an erect (within 15 seconds of standing) BP measurement were recorded. Participants recorded whether they felt dizzy on standing. A mixed-effect model was used to test for a difference in the change in BP for time and altitude. The immediate fall in systolic BP observed on standing was significantly greater (P < .001) on all 3 altitude study days (18.2, 23.4, and 20.7 mm Hg) than at sea level (12.2 and 12.4 mm Hg). There was no significant difference in the change in diastolic BP or change in mean arterial BP between sea level and altitude. The immediate drop in systolic BP observed on standing was greater at altitude. However, mean arterial pressure was maintained, and we found no association between the degree of immediate fall in BP and dizziness or AMS.

Functional changes in baroreceptor afferent, central and efferent components of the baroreflex circuitry in type 1 diabetic mice (OVE26)

Baroreflex control of heart rate (HR) is impaired in diabetes mellitus. We hypothesized that diabetes mellitus induced functional changes of neural components at multiple sites within the baroreflex arc. Type 1 diabetic mice (OVE26) and FVB control mice were anesthetized. Baroreflex-mediated HR responses to sodium nitroprusside- (SNP) and phenylephrine- (PE) induced mean arterial blood pressure (MAP) changes were measured. Baroreceptor function was characterized by measuring the percent (%) change of baseline integrated aortic depressor nerve activity (Int ADNA) in response to SNP- and PE-induced MAP changes. The HR responses to electrical stimulation of the left aortic depressor nerve (ADN) and the right vagus nerve were assessed. Compared with FVB control mice, we found in OVE26 mice that (1) baroreflex-mediated bradycardia and tachycardia were significantly reduced. (2) The baroreceptor afferent function in response to MAP increase did not differ, as assessed by the parameters of the logistic function curve. But, the inhibition of Int ADNA in response to MAP decrease was significantly attenuated. (3) The maximum amplitude of bradycardic responses to right vagal efferent stimulation was augmented. (4) In contrast, the maximum amplitude of bradycardic responses to left ADN stimulation was decreased. Since Int ADNA was preserved in response to MAP increase and HR responses to vagal efferent stimulation were augmented, we conclude that a deficit of the central mediation of baroreflex HR contributes to the overall attenuation of baroreflex sensitivity in OVE26 mice. The successful conduction of physiological experiments on the ADN in OVE26 mice may provide a foundation for the understanding of cellular and molecular mechanisms of diabetes-induced cardiac neuropathy.

Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo

We demonstrated previously that reciprocal regulation of soluble (sGC) and particulate (pGC) guanylate cyclases by NO and natriuretic peptides coordinates cyclic cGMP-mediated vasodilatation in vitro. Herein, we investigated whether such an interaction contributes to vascular homeostasis in mice and humans in vivo. Mean arterial blood pressure (MABP) changes in anaesthetized mice were monitored in response to i.v. administration of cGMP- and cAMP-dependent vasodilators in wild-type (WT), endothelial NO synthase (eNOS) and natriuretic peptide receptor (NPR)-A knockout mice. Forearm blood flow (FBF) in response to intra-brachial infusion of ANP (25, 50, 100, 200 pmol min(-1)) in the absence and presence of the NOS inhibitor NG-methyl-L-arginine (L-NMA; 4 micromol min(-1)) and the control constrictor noradrenaline (240 pmol min(-1)) was assessed in healthy volunteers. Sodium nitroprusside (SNP; NO-donor) and atrial natriuretic peptide (ANP) produced dose-dependent reductions in MABP in WT animals that were significantly enhanced in eNOS KO mice. In NPR-A K mice, SNP produced a dose-dependent reduction in MABP that was significantly greater than that in WT mice. Responsiveness to the cAMP-dependent vasodilator epoprostenol was similar in WT, eNOS KO and NPR-A KO animals. ANP caused vasodilatation of the forearm resistance vasculature that was significantly greater in individuals lacking endothelium-derived NO (i.e. L-NMA treated). These data demonstrate that crosstalk occurs between the NO-sGC and ANP-pGC pathways to regulate cGMP-dependent vasodilatation in vivo in both mice and humans. These findings have implications for understanding the link between natriuretic peptide activity and cardiovascular risk.

Maternal Androgen and Estrogen Concentrations Are Not Associated with Blood Pressure Changes in Uncomplicated Pregnancies

Systolic blood pressure increase between the second and third trimester of pregnancy has been associated with a substantially reduced maternal breast cancer risk, and it has been suggested that elevated androgens mediate the association. Androgen and estrogen concentrations were measured in maternal serum collected in 86 uncomplicated, singleton pregnancies. Overall, there were no consistent or statistically significant patterns of association between the hormones and systolic, diastolic, or mean arterial blood pressure or blood pressure change between trimesters. Results were similar with adjustment for factors related to the hormones. These data are not consistent with the hypothesis that elevated androgen concentrations mediate the observed reduction in maternal breast cancer risk associated with increases in blood pressure over the pregnancy.

Angiotensin II Decreases the Renal MRI Blood Oxygenation Level–Dependent Signal

Acute experimental reduction of renal blood flow decreases the renal blood oxygenation level-dependent (BOLD) MRI signal in animals. Angiotensin II also reduces renal blood flow, but the ability of BOLD MRI to dynamically detect this response has not yet been investigated in humans. Six healthy male volunteers underwent an individual dose-finding study to identify the intravenous doses of angiotensin II, norepinephrine, and sodium nitroprusside necessary to induce a 15-mm Hg peak mean arterial blood pressure change. MRI studies followed within 3 weeks, when angiotensin II (8.8+/-1.4 ng/kg), norepinephrine (52+/-12 ng/kg), and sodium nitroprusside (2.0+/-0.3 microg/kg) were given twice in an unblocked, randomized sequence while imaging experiments were performed on a 1.5-T Siemens Sonata. A multiecho echo-planar imaging sequence was used to acquire T2* maps with a temporal resolution of 1 respiratory cycle. Averaged over a renal cortex dominated region of interest, angiotensin II caused a shortening of T2* between 6% and 10%. Sodium nitroprusside and norepinephrine, although of equal potency concerning blood pressure responses, did not alter the renal BOLD signal. The renal BOLD response to angiotensin II appeared with short onset latency (as early as 10 seconds after peripheral intravenous angiotensin II bolus administration) suggesting that this response is a consequence of altered perfusion rather than increased renal oxygen consumption. The methods described here are suitable to assess renal responsiveness to angiotensin II and may, thus, be of great value in human hypertension research.