Changes in sympathetic nervous system activity after renal denervation: results from the randomised Oslo RDN study.

PURPOSE: Sympathetic nervous system (SNS) over-activity is associated with essential hypertension. Renal sympathetic denervation (RDN) possibly lowers office- and ambulatory blood pressure (BP) in patients with treatment-resistant hypertension (TRH). We aimed to assess the effect of RDN compared to drug adjustment on SNS activity among patients with TRH by measuring plasma catecholamines and heart rate variability (HRV) during stress tests. MATERIALS AND METHODS: Patients with TRH were randomised to RDN (n = 9) or Drug Adjustment (DA) (n = 10). We measured continuous HRV and beat-to-beat-BP using FinaPres® and obtained plasma catecholamines during standardised orthostatic- and cold-pressor stress tests (CPT) before- and six months after randomisation. RESULTS: CPT revealed no differences between groups at baseline in peak adrenaline concentration (69.3 pg/mL in the DA group vs. 70.0 pg/mL in the RDN group, p = 0.38) or adrenaline reactivity (Δ23.1 pg/mL in the DA group vs. Δ29.3 pg/mL in the RDN group, p = 0.40). After six months, adrenaline concentrations were statistically different between groups after one minute (66.9 pg/mL in the DA group vs. 55.3 pg/mL in the RDN group, p = 0.03), and six minutes (62.4 pg/mL in the DA group vs. 50.1 pg/mL in the RDN group, p = 0.03). There was a tendency of reduction in adrenaline reactivity after six months in the RDN group (Δ26.3 pg/mL at baseline vs. Δ12.8 pg/ml after six months, p = 0.08), while it increased in the DA group (Δ13.6 pg/mL at baseline vs. Δ19.9 pg/mL after six months, p = 0.53). We also found a difference in the Low Frequency band at baseline following the CPT (667µs2 in the DA group vs. 1628µs2 in the RDN group, p = 0.03) with a clear tendency of reduction in the RDN group to 743µs2 after six months (p = 0.07), compared to no change in the DA group (1052µs2,p = 0.39). CONCLUSION: Our data suggest that RDN reduces SNS activity after six months. This finding warrants investigation in a larger study. Clinical Trial Number registered at www.clinicaltrials.gov: NCT01673516.

Chronic pain-related changes in cardiovascular regulation and impact on comorbid hypertension in a general population: the Tromsø study.

Heart rate variability (HRV) and baroreflex sensitivity (BRS) are indexes reflecting the ability to maintain cardiovascular homeostasis amidst changing conditions. Evidence primarily from small studies suggests that both HRV and BRS may be reduced in individuals with chronic pain (CP), with potential implications for cardiovascular risk. We compared HRV and BRS between individuals with CP (broadly defined) and pain-free controls in a large unselected population sample. Participants were 1143 individuals reporting clinically meaningful CP and 5640 pain-free controls who completed a 106-second cold pressor test (CPT). Participants self-reported hypertension status. Resting HRV and BRS were derived from continuous beat-to-beat blood pressure recordings obtained before and after the CPT. Hierarchical regressions for the pre-CPT period indicated that beyond effects of age, sex, and body mass index, the CP group displayed significantly lower HRV in both the time domain (SDNN and rMSSD) and frequency domain (high-frequency HRV power), as well as lower BRS. Results were somewhat weaker for the post-CPT period. Mediation analyses indicated that for 6 of 7 HRV and BRS measures tested, there were significant indirect (mediated) effects of CP status on the presence of comorbid hypertension via reduced HRV or BRS. Results confirm in the largest and broadest sample tested to date that the presence of CP is linked to impaired cardiovascular regulation and for the first time provide support for the hypothesis that links between CP and comorbid hypertension reported in previous population studies may be due in part to CP-related decrements in cardiovascular regulation.

Increased heart rate variability during nondirective meditation.

PURPOSE: Meditation practices are in use for relaxation and stress reduction. Some studies indicate beneficial cardiovascular health effects of meditation. The effects on the autonomous nervous system seem to vary among techniques. The purpose of the present study was to identify autonomic nerve activity changes during nondirective meditation. MATERIALS AND METHODS: Heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) were monitored in 27 middle-aged healthy participants of both genders, first during 20 min regular rest with eyes closed, thereafter practising Acem meditation for 20 min. Haemodynamic and autonomic data were collected continuously (beat-to-beat) and non-invasively. HRV and BPV parameters were estimated by power spectral analyses, computed by an autoregressive model. Spontaneous activity of baroreceptors were determined by the sequence method. Primary outcomes were changes in HRV, BPV, and BRS between rest and meditation. RESULTS: HRV increased in the low-frequency (LF) and high-frequency (HF) bands during meditation, compared with rest (p = 0.014, 0.013, respectively). Power spectral density of the RR-intervals increased as well (p = 0.012). LF/HF ratio decreased non-significantly, and a reduction of LF-BPV power was observed during meditation (p < 0.001). There was no significant difference in BRS. Respiration and heart rates remained unchanged. Blood pressure increased slightly during meditation. CONCLUSION: There is an increased parasympathetic and reduced sympathetic nerve activity and increased overall HRV, while practising the technique. Hence, nondirective meditation by the middle aged may contribute towards a reduction of cardiovascular risk.

Effects on plasma noradrenaline may explain some of the improved insulin sensitivity seen by AT-1 receptor blockade.

AIMS: We have previously found improved insulin sensitivity in hypertensives after additional treatment with angiotensin II-receptor blocker (ARB) compared with calcium-channel blocker (CCB) alone, despite similar blood pressure lowering effects. In this study, we compare the effect of these two principal different vasodilating agents on the autonomic nervous system in the same patients, and test whether potential differences in these variables might explain the difference seen in insulin sensitivity. METHODS: In a double-blind crossover study, 21 hypertensive patients were randomized to receive either 100 mg losartan (ARB) or 5 mg amlodipine (CCB) in addition to an open-labelled treatment of amlodipine 5 mg. The patients were treated for 8 weeks with either treatment regimens after a 4-week run-in and a 4-week washout period. Plasma catecholamines were measured using radioenzymatic technique and baroreflex sensitivity and heart rate variability was tested at rest and during 24-h ECG registration. RESULTS: Plasma noradrenaline was significantly lower after additional treatment with ARB compared with CCB alone (304+/-29 pg/ml vs 373+/-43 pg/ml, p = 0.022). Heart rate variability, baroreflex sensitivity or plasma adrenaline did not differ significantly between the two treatment regimens. CONCLUSION: The results may suggest that improvement of insulin sensitivity by ARB is related to decreased plasma noradrenaline and potential sympatholytic effects.

Ventricular fibrillation induced by ischemia-reperfusion is not prevented by the NPY Y2 receptor antagonist BIIE0246.

Neuropeptide Y is released together with norepinephrine from sympathetic nerve terminals during conditions of increased sympathetic activity. Neuropeptide Y is known to inhibit vagal activity, and accordingly, it might increase the risk for ventricular fibrillation during myocardial ischemia-reperfusion, with concomitant sympathetic stimulation. Counteracting the inhibiting effect of neuropeptide Y by the specific neuropeptide Y2 antagonist, BIIE0246, we expected occurrence of ventricular fibrillation in association with repeated periods of myocardial ischemia-reperfusion to decrease. The midleft anterior descending coronary artery was repeatedly occluded in 16 open-chest pigs. Eight pigs received BIIE0246, and the controls received the vehicle only. Ventricular fibrillation developed in 2 animals of the control group, but in 4 pigs receiving BIIE0246. Occurrence of ventricular fibrillation and ventricular tachycardia did not differ significantly between the 2 groups, and in association with repeated periods of regional myocardial ischemia, did not decline in pigs treated by the specific neuropeptide Y2-receptor antagonist BIIE0246.

Adrenaline during mental stress in relation to fitness, metabolic risk factors and cardiovascular responses in young men.

We studied plasma adrenaline (A) in relation to physical fitness, metabolic cardiovascular risk factors and cardiovascular responses. Men (age 21-24 years) with high and normal (both n=19) screening blood pressure (BP) were studied cross-sectionally. We measured peak oxygen uptake (VO2peak) (treadmill exercise), and plasma catecholamines, heart rate (HR), finger systolic (SBP) and diastolic (DBP) BP, and insulin-adjusted glucose disposal rate (GDR/I) during a hyperinsulinaemic glucose clamp (rest) and mental arithmetic stress test (MST). By multiple regression, A at rest (Arest) (beta=0.37, p<0.05) and during MST (Amst) (beta=0.40, p<0.01) were associated with high screening BP. In the respective models, Arest was negatively related to body mass index (BMI) (beta=-0.56, p<0.001) and Amst positively to VO2peak (beta=0.54, p<0.001). BP and HR responses correlated positively with VO2peak, but were determined by Amst in multiple regression models. Independently of BMI and VO2peak, serum high-density lipoprotein cholesterol was positively related to A levels, whereas GDR/I was independently related only to VO2peak. Increased adrenaline secretion may be related to high BP, but may at the same time be associated with a beneficial metabolic profile.

Blood viscosity: effects of mental stress and relations to autonomic nervous system function and insulin sensitivity.

We studied effects of mental stress on whole-blood viscosity (WBV) and blood pressure (BP), and relations between WBV and autonomic nervous system activity and insulin sensitivity. We measured WBV (rotational rheometer), plasma noradrenaline (NA), finger BP, heart rate variability (HRV) and baroreflex sensitivity (BRS; transfer technique) during hyperinsulinaemic glucose clamp and mental arithmetic stress test (MST) in 20 men with high ( > or =140/90 mmHg) and 21 men with normal (< or =115/75 mmHg) screening BP, and 10 women regardless of screening BP (all normotensive). WBV and NA increased during the MST, while HRV and BRS decreased. During the MST, WBV (all shear rates) and the response ((delta)WBV) (low shear) were higher in men with high compared to normal screening BP (p<0.05). In men, WBV correlated positively with NA and negatively with HRV, BRS and insulin sensitivity. The diastolic BP response ((delta)DBP) was independently explained by high-shear (delta)WBV (p<0.05) and (delta)NA (p<0.0001), and (delta)WBV independently by (delta)DBP (p<0.05). WBV is related to increased sympathetic activity, impaired vagal cardiac control and low insulin sensitivity in young adults. The haemorheological effect of mental stress is increased in young men with high screening BP and may be mediated by the acute increase in BP.

Plasma catecholamines, blood pressure responses and perceived stress during mental arithmetic stress in young men.

We assessed plasma noradrenaline (NA) and adrenaline (A) at rest during a hyperinsulinaemic glucose clamp and responses to a mental arithmetic stress test (MST) in relation to blood pressure (BP) responses (Finapres) and distress in 20 men with high (> or =140/90 mmHg) and 21 men with normal (< or =115/75 mmHg) screening BP, 21-24 years of age. Perceived stress, effort and overall discomfort were scored 1-10. Catecholamines and BP increased in both groups, change in diastolic BP (DeltaDBP; 9.9 vs. 3.8 mmHg, p < 0.05) and DeltaDBP carryover (recovery period minus baseline) (7.2 vs. 2.2 mmHg, p < 0.01) being greater in men with high screening BP. Independently of BP status, change in systolic BP (DeltaSBP) and DeltaSBP carryover were related to A (both p < 0.001), and DeltaDBP and DeltaDBP carryover to DeltaNA (both p < 0.001). The subjective score sum correlated with maximal NA (rs = 0.40) and A (rs = 0.37) (both p < 0.05). Maximal NA was independently related to stress (p < 0.05) and the subjective score sum (p < 0.01). DeltaA% was greater in the high- (score > or =6) than in the low-stress category, independently of BP status (p < 0.05). High screening BP is associated with impaired BP recovery after mental stress. Plasma catecholamine responses are related to BP responses and carryover effects, and reflect perceived stress in young men.

Relations between insulin sensitivity, fitness and autonomic cardiac regulation in healthy, young men.

OBJECTIVES: We hypothesized that insulin sensitivity and vagal cardiac control are independently related in young men after adjustment for fitness and other confounding variables. DESIGN: Male volunteers aged 21-24 years with high (borderline hypertensive; n = 20) and low-normal (normotensive; n = 21) screening blood pressure (BP) were studied cross-sectionally. METHODS: Mean R-R interval (RR) and heart rate variability (HRV) were computed from 30-min ECGs, and baroreflex sensitivity (BRS) and latency (phase shift) from 15-min beat-to-beat finger blood pressure (BP) and heart rate recordings. Insulin-adjusted glucose disposal rate (GDR/I) was measured with a 90-min hyperinsulinaemic glucose clamp and fitness by peak oxygen uptake (VO2peak) during a treadmill test. RESULTS: HRV, baroreflex function, GDR/I, and VO2peak did not differ between the groups. GDR/I correlated positively with time and frequency domain HRV, including high-frequency power (HF) (r = 0.40, P = 0.01) and root-mean squared successive differences (RMSSD) (r = 0.43, P = 0.005), but not BRS or phase shift. GDR/I correlated with VO2peak (r = 0.70, P < 0.0001) and was explained (R = 0.56) by VO2peak (beta = 0.57, P < 0.0001) and RR (beta = 0.29, P = 0.03), independently of HRV and measures of obesity. Conversely, RR (beta = 0.55, P = 0.0004) and HRV, including HF (beta = 0.44, P = 0.006) and RMSSD (beta = 0.46, P = 0.004) were explained by GDR/I, independently of VO2peak. CONCLUSIONS: Insulin sensitivity and autonomic cardiac control are related independently of physical fitness in young men.

Reduced baroreceptor reflex sensitivity and increased blood pressure variability at 2400 m simulated cabin altitude.

In a hypobaric chamber nine healthy volunteers were exposed to an atmospheric pressure corresponding to 2400 m above sea level. This is similar to the lowest air pressure encountered inside pressurized commercial airplanes. Heart rate and blood pressure were monitored beat-to-beat in the supine position with a non-invasive device. Blood pressure variability and heart rate variability were measured in the mid-frequency band; subsequently, baroreceptor reflex sensitivity (BRS) was calculated with the transfer-function method. Compared with baseline, there were reduced BRS and increased blood pressure variability at 2400 m (16.5 +/- 3.1 vs. 13.2 +/- 2.0 ms x mm Hg(-1) and 5.4 +/- 1.3 vs. 8.2 +/- 1.1 mm Hg, respectively; p < 0.05). We conclude that autonomic cardiovascular control was disturbed during acute exposure to an air pressure corresponding to 2400 m.