Isometric handgrip training reduces arterial pressure at rest without changes in sympathetic nerve activity

The purpose of this study was to determine whether isometric handgrip (IHG) training reduces arterial pressure and whether reductions in muscle sympathetic nerve activity (MSNA) mediate this drop in arterial pressure. Normotensive subjects were assigned to training (n = 9), sham training (n = 7), or control (n = 8) groups. The training protocol consisted of four 3-min bouts of IHG exercise at 30% of maximal voluntary contraction (MVC) separated by 5-min rest periods. Training was performed four times per week for 5 wk. Subjects' resting arterial pressure and heart rate were measured three times on 3 consecutive days before and after training, with resting MSNA (peroneal nerve) recorded on the third day. Additionally, subjects performed IHG exercise at 30% of MVC to fatigue followed by muscle ischemia. In the trained group, resting diastolic (67 +/- 1 to 62 +/- 1 mmHg) and mean arterial pressure (86 +/- 1 to 82 +/- 1 mmHg) significantly decreased, whereas systolic arterial pressure (116 +/- 3 to 113 +/- 2 mmHg), heart rate (67 +/- 4 to 66 +/- 4 beats/min), and MSNA (14 +/- 2 to 15 +/- 2 bursts/min) did not significantly change following training. MSNA and cardiovascular responses to exercise and postexercise muscle ischemia were unchanged by training. There were no significant changes in any variables for the sham training and control groups. The results indicate that IHG training is an effective nonpharmacological intervention in lowering arterial pressure.     

Physical activity and blood pressure in normotensive young women

Blood pressure and heart rate were measured in 22 physically active normotensive women, 20 +/- 1.7 years old (mean +/- SD) and in 25 physically non-active normotensive women 20.9 +/- 1.7 years old in supine, sitting and standing positions. Diastolic and mean blood pressures were found to be significantly lower in active women than non-active women. A significant negative correlation was found between maximal oxygen consumption and blood pressure, and it is suggested that aerobic physical activity could be used as non-pharmacological therapy in cases of moderate and borderline hypertension in young women.     

NO inhalation reduces pulmonary arterial pressure but not hemorrhage in maximally exercising horses.

In horses, the exercise-induced elevation of pulmonary arterial pressure (Ppa) is thought to play a deterministic role in exercise-induced pulmonary hemorrhage (EIPH), and thus treatment designed to lower Ppa might reasonably be expected to reduce EIPH. Five Thoroughbred horses were run on a treadmill to volitional fatigue (incremental step test) under nitric oxide (NO; inhaled 80 ppm) and control (N(2), same flow rate as per NO run) conditions (2 wk between trials; order randomized) to test the hypothesis that NO inhalation would reduce maximal Ppa but that this reduction may not necessarily reduce EIPH. Before each investigation, a microtipped pressure transducer was placed in the pulmonary artery 8 cm past the pulmonic valve to monitor Ppa. EIPH severity was assessed via bronchoalveolar lavage (BAL) 30 min postrun. Exercise time did not differ between the two trials (P > 0.05). NO administration resulted in a small but consistent and significant reduction in peak Ppa (N(2), 102.3 +/- 4.4; NO, 98.6 +/- 4.3 mmHg, P < 0.05). In the face of lowered Ppa, EIPH severity was significantly higher in the NO trial (N(2), 22.4 +/- 6.8; NO, 42.6 +/- 15.4 x 10(6) red blood cells/ml BAL fluid, P < 0.05). These findings support the notion that extremely high Ppa may reflect, in part, an arteriolar vasoconstriction that serves to protect the capillary bed from the extraordinarily high Ppa evoked during maximal exercise in the Thoroughbred horse. Furthermore, these data suggest that exogenous NO treatment during exercise in horses may not only be poor prophylaxis but may actually exacerbate the severity of EIPH.     

Sympathetic activation increases basilar arterial blood flow in normotensive but not hypertensive rats

The close apposition between sympathetic and parasympathetic nerve terminals in the adventitia of cerebral arteries provides morphological evidence that sympathetic nerve activation causes parasympathetic nitrergic vasodilation via a sympathetic-parasympathetic interaction mechanism. The decreased parasympathetic nerve terminals in basilar arteries (BA) of spontaneously hypertensive rat (SHR) and renovascular hypertensive rats (RHR) compared with Wistar-Kyoto rats (WKY), therefore, would diminish this axo-axonal interaction-mediated neurogenic vasodilation in hypertension. Increased basilar arterial blood flow (BABF) via axo-axonal interaction during sympathetic activation was, therefore, examined in anesthetized rats by laser-Doppler flowmetry. Electrical stimulation (ES) of sympathetic nerves originating in superior cervical ganglion (SCG) and topical nicotine (10-30 μM) onto BA of WKY significantly increased BABF. Both increases were inhibited by tetrodotoxin, 7-nitroindazole (neuronal nitric oxide synthase inhibitor), and ICI-118,551 (β(2)-adrenoceptor antagonist), but not by atenolol (β(1)-adrenoceptor antagonist). Topical norepinephrine onto BA also increased BABF, which was abolished by atenolol combined with 7-nitroindazole or ICI-118,551. Similar results were found in prehypertensive SHR. However, in adult SHR and RHR, ES of sympathetic nerves or topical nicotine caused minimum or no increase of BABF. It is concluded that excitation of sympathetic nerves to BA in WKY causes parasympathetic nitrergic vasodilation with increased BABF. This finding indicates an endowed functional neurogenic mechanism for increasing the BABF or brain stem blood flow in coping with increased local sympathetic activities in acutely stressful situations such as the "fight-or-flight response." This increased blood flow in defensive mechanism diminishes in genetic and nongenetic hypertensive rats due most likely to decreased parasympathetic nitrergic nerve terminals.     

Strength training,but not endurance training,reduces motor unit discharge rate variability

This study evaluates and compares the effects of strength and endurance training on motor unit discharge rate variability and force steadiness of knee extensor muscles. Thirty sedentary healthy men (age, 26.0 ± 3.8 yrs) were randomly assigned to strength training, endurance training or a control group. Conventional endurance and strength training was performed 3 days per week, over a period of 6 weeks. Maximum voluntary contraction (MVC), time to task failure (at 30% MVC), coefficient of variation (CoV) of force and of the discharges rates of motor units from the vastus medialis obliquus and vastus lateralis were determined as subjects performed 20% and 30% MVC knee extension contractions before and after training. CoV of motor unit discharges rates was significantly reduced for both muscles following strength training (P < 0.001), but did not change in the endurance (P = 0.875) or control group (P = 0.995). CoV of force was reduced after the strength training intervention only (P < 0.01). Strength training, but not endurance training, reduces motor unit discharge rate variability and enhances force steadiness of the knee extensors. These results provide new insights into the neuromuscular adaptations that occur with different training methods.     

The effects of cigarette smoking on intraocular pressure and arterial blood pressure of normotensive young Nigerian male adults.

This study was designed to determine the effects of cigarette Smoking on intra ocular pressure and arterial blood pressure of normotensive young male adults. Fifty male students (who met the screening conditions and devoid of obvious ocular pathology and systemic diseases and non-smokers) had their intra ocular pressure (IOP) measured with a schiotz tonometer and blood pressure(BP) measured with standard syphgmomanometer respectively prior to smoking of two sticks of cigarette each day for one month and thereafter. The result showed a significant [P < 0.01] effect on the intra ocular pressure with a mean control of 37.76 +/- 0.98 for both eyes and test of 41.93 +/-0.98. Cigarette smoking increased the blood pressure from mean control of 197.24 +/-0.88 to 208.46 +/-0.82. The increase of both intra ocular pressure and arterial blood pressure was due to nicotine, the principal constituent of cigarette. It is recommended that health care workers should check regularly the IOP and BP of their cigarette smoking patients for early diagnoses of ocular hypertension (glaucoma) and hypertension.     

Increasing oxidative stress with molsidomine increases blood pressure in genetically hypertensive rats but not normotensive controls

Spontaneously hypertensive rats (SHR) have a higher level of oxidative stress and exhibit a greater depressor response to a superoxide scavenger, tempol, than normotensive Wistar-Kyoto rats (WKY). This study determined whether an increase in oxidative stress with a superoxide/NO donor, molsidomine, would amplify the blood pressure in SHR. Male SHR and WKY were given molsidomine (30 mg.kg(-1).day(-1)) or vehicle (0.01% ethanol) for 1 wk, and blood pressure, renal hemodynamics, nitrate and nitrite excretion (NOx), renal superoxide production, and expression of renal antioxidant enzymes, Mn- and Cu,Zn-SOD, catalase, and glutathione peroxidase (GPx), were measured. Renal superoxide and NOx were higher in control SHR than in WKY. Molsidomine increased superoxide by approximately 35% and NOx by 250% in both SHR and WKY. Mean arterial blood pressure (MAP) was also higher in control SHR than WKY. Molsidomine increased MAP by 14% and caused renal vasoconstriction in SHR but reduced MAP by 16%, with no effect on renal hemodynamics, in WKY. Renal expression of Mn- and Cu,Zn-SOD was not different between SHR and WKY, but expression of catalase and GPx were approximately 30% lower in kidney of SHR than WKY. The levels of Mn- and Cu,Zn-SOD were not increased with molsidomine in either WKY or SHR. Renal catalase and GPx expression was increased by 300-400% with molsidomine in WKY, but there was no effect in SHR. Increasing oxidative stress elevated blood pressure further in SHR but not WKY. WKY are likely protected because of higher bioavailable levels of NO and the ability to upregulate catalase and GPx.     

Intrathecal PACAP-38 causes increases in sympathetic nerve activity and heart rate but not blood pressure in the spontaneously hypertensive rat

The rostral ventrolateral medulla contains presympathetic neurons that project monosynaptically to sympathetic preganglionic neurons (SPN) in the spinal cord and are essential for the tonic and reflex control of the cardiovascular system. SPN directly innervate the adrenal medulla and, via postganglionic axons, affect the heart, kidneys, and blood vessels to alter sympathetic outflow and hence blood pressure. Over 80% of bulbospinal, catecholaminergic (C1) neurons contain pituitary adenylate cyclase-activating polypeptide (PACAP) mRNA. Activation of PACAP receptors with intrathecal infusion of PACAP-38 causes a robust, prolonged elevation in sympathetic tone. Given that a common feature of most forms of hypertension is elevated sympathetic tone, this study aimed to determine in the spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (normotensive control) 1) the proportion of C1 neurons containing PACAP mRNA and 2) responsiveness to intrathecal PACAP-38. We further investigated whether intrathecal infusion of the PACAP antagonist, PACAP(6-38), reduces the hypertension in the SHR. The principal findings are that 1) the proportion of PACAP mRNA-containing C1 neurons is not different between normotensive and hypertensive rats, 2) intrathecal PACAP-38 causes a strain-dependent, sustained sympathoexcitation and tachycardia with variable effects on mean arterial pressure in normotensive and hypertensive rats, and 3) PACAP(6-38) effectively attenuated the effects of intrathecal PACAP-38, but had no effect alone, on any baseline variables. This finding indicates that PACAP-38 is not tonically released in the spinal cord of rats. A role for PACAP in hypertension in conscious rats remains to be determined.     

Intracerebroventricular injection of hemicholinium-3 lowers blood pressure in conscious spontaneously hypertensive rats but not in normotensive rats

Intracerebroventricular (icv) injection of hemicholinium-3 (HC-3) in doses of 10–20 μg causes a dose-related decrease in the blood pressure of conscious spontaneous hypertensive (SH) rats but not of normotensive rats. HC-3 also reduces heart rate (HR) in both SH and normotensive rats. The bradycardia was blocked by intravenous injection of methylatropine, implicating increased vagal activity as a cause of the response. The decrease in HR also was blocked by icv injection of atropine but not by icv injection of mecamylamine, suggesting that the bradycardia is mediated via central muscarinic receptors. In contrast, the fall in blood pressure in SH rats was not influenced by intravenous administration of methylatropine or by the icv injection of either atropine or mecamylamine.     

The effect of specific hypnotic suggestions on blood pressure in normotensive subjects

Twenty normotensive subjects participated on a voluntary basis in an experiment designed to study the effects of specific suggestions on blood pressure (BP). After an induction procedure, the experimental group received suggestions presumed to be relatively nonactivating, although capable of lowering or raising BP. A control group was used to record the BP changes over time. All subjects met for one session. Eight subjects from the experimental group met for a second session. Both adaptation and induction resulted in significant BP decreases. A specific suggestion to increase BP gave a significant result when compared to the induction point. There was no significant change from induction to the BP decrease suggestion. Both systolic and diastolic BP behaved in the same way. A second experimental session resulted in no significant change compared with the first session. Also, no significant difference was found in suggestibility scores from the first to the second session. The results are in line with previously published studies.     

Noninvasive, automatic 24-h ambulatory blood pressure monitoring in normotensive subjects

The reliability of noninvasive, automatic blood pressure monitoring is not yet clearly established. A 24-h ambulatory blood pressure profile was obtained in 9 healthy, normotensive subjects with an automatic, noninvasive device. The blood pressure profile showed the typical circadian pattern with lower systolic and diastolic values during sleep, although pulse pressure was fairly constant (about 40 mm Hg). The systolic blood pressure rose steeply in the early morning hours--before waking up. The results were compared with simultaneous hourly readings using the auscultatory method. There were no statistically significant differences between the automatic and auscultatory readings, 13 of the 18 mean values at different time points being within 2 mm Hg of each other. All the auscultatory means fell within the 95% confidence limits of those measured hourly by the automatic method. Although the automatic method seemed to be reliable compared with the auscultatory method, its sensitivity to motion artifacts is a disadvantage in a truly ambulatory setting.     

Acute arterial hypertension inhibits proximal tubular fluid reabsorption in normotensive rat but not in SHR

The effect of acute arterial hypertension on proximal tubular fluid reabsorption was investigated in Sprague-Dawley rats and spontaneously hypertensive rats (SHR) by measuring proximal tubular flow with a nonobstructive optical method. Under control conditions, spontaneous tubular flow was oscillating at 0.02-0.03 Hz in Sprague-Dawley rats. Acute hypertension induced an immediate increase of mean tubular flow (50% increase after 20 min of hypertension) and augmentation of oscillatory amplitude. Acute hypertension did not alter single-nephron blood flow as measured by laser-Doppler velocimetry (n = 12), suggesting that the increase of tubular flow was due to inhibition of reabsorption but not increase of filtration. By contrast, spontaneous tubular flow was fluctuating aperiodically in SHR. Acute hype tension did not induce a continuous increase of tubular flow or an increase in amplitude of fluctuations (n = 15). When apical Na(+)/H(+) exchange activity of proximal tubule was monitored, acute hypertension did not alter the activity in SHR (n = 8), while similar procedures had been shown to inhibit apical Na(+)/H(+) exchange activity of proximal tubules by more than 40% in Sprague-Dawley rats. These observations suggest that acute hypertension inhibits proximal tubular fluid reabsorption by inhibiting apical Na(+)/H(+) exchange activity in Sprague-Dawley rats and that this mechanism is impaired in SHR.     

Hypoxemia raises muscle sympathetic activity but not norepinephrine in resting humans

The experimental objective was to determine whether moderate to severe hypoxemia increases skeletal muscle sympathetic nervous activity (MSNA) in resting humans without increasing venous plasma concentrations of norepinephrine (NE) and epinephrine (E). In nine healthy subjects (20-34 yr), we measured MSNA (peroneal nerve), venous plasma levels of NE and E, arterial blood pressure, heart rate, and end-tidal O2 and CO2 before (control) and during breathing of 1) 12% O2 for 20 min, 2) 10% O2 for 20 min, and 3) 8% O2 for 10 min--in random order. MSNA increased above control in five, six, and all nine subjects during 12, 10, and 8% O2, respectively (P less than 0.01), but only after delays of 12 (12% O2) and 4 min (8 and 10% O2). MSNA (total activity) rose 83 +/- 20, 260 +/- 146, and 298 +/- 109% (SE) above control by the final minute of breathing 12, 10, and 8% O2, respectively. NE did not rise above control at any level of hypoxemia; E rose slightly (P less than 0.05) at one time only with both 10 and 8% O2. Individual changes in MSNA during hypoxemia were unrelated to elevations in heart rate or decrements in blood pressure and end-tidal CO2--neither of which always fell. We conclude that in contrast to some other sympathoexcitatory stimuli such as exercise or cold stress, moderate to severe hypoxemia increases leg MSNA without raising plasma NE in resting humans.     

Pre-meal water consumption reduces meal energy intake in older but not younger subjects

Objective: To determine whether the consumption of water 30 minutes before an ad libitum meal reduces meal energy intake in young and older adults. Research Methods and Procedures: Healthy, non‐obese young (n = 29; age, 21 to 35 years) and older (n = 21; age, 60 to 80 years) individuals were provided with an ad libitum lunch meal on two occasions. Thirty minutes before the lunch meals, subjects were given either a water preload (WP: 375 mL, women; 500 mL, men) or no preload (NP). Energy intake at the two lunch meals was measured. Visual analog scales were used to assess changes in hunger, fullness, and thirst during the meal studies. Results: There was no significant difference in meal energy intake between conditions in the young subjects (892 + 51 vs. 913 ± 54 kcal for NP and WP, respectively; p = 0.65). However, meal energy intake after the WP was significantly reduced relative to the NP condition in the older subjects (682 + 53 vs. 624 ± 56 kcal for NP and WP, respectively; p = 0.02). This effect was caused primarily by the reduction in meal energy intake after water consumption in older men. Hunger ratings were lower and fullness ratings were higher in older compared with younger adults (p < 0.01). Fullness ratings were higher in the WP condition compared with the NP condition for all subjects (p = 0.01). No age differences in thirst were detected during the test meals. Discussion: Under acute test meal conditions, pre‐meal water consumption reduces meal energy intake in older but not younger adults. Because older adults are at increased risk for overweight and obesity, intervention studies are needed to determine whether pre‐meal water consumption is an effective long‐term weight management strategy for the aging population.     

Acute inhibition of PMCA4, but not global ablation,reduces blood pressure and arterial contractility via a nNOS‐dependent mechanism

Cardiovascular disease is the world's leading cause of morbidity and mortality, with high blood pressure (BP) contributing to increased severity and number of adverse outcomes. Plasma membrane calcium ATPase 4 (PMCA4) has been previously shown to modulate systemic BP. However, published data are conflicting, with both overexpression and inhibition of PMCA4 in vivo shown to increase arterial contractility. Hence, our objective was to determine the role of PMCA4 in the regulation of BP and to further understand how PMCA4 functionally regulates BP using a novel specific inhibitor to PMCA4, aurintricarboxylic acid (ATA). Our approach assessed conscious BP and contractility of resistance arteries from PMCA4 global knockout (PMCA4KO) mice compared to wild‐type animals. Global ablation of PMCA4 had no significant effect on BP, arterial structure or isolated arterial contractility. ATA treatment significantly reduced BP and arterial contractility in wild‐type mice but had no significant effect in PMCA4KO mice. The effect of ATAin vivo and ex vivo was abolished by the neuronal nitric oxide synthase (nNOS) inhibitor Vinyl‐l ‐NIO. Thus, this highlights differences in the effects of PMCA4 ablation and acute inhibition on the vasculature. Importantly, for doses here used, we show the vascular effects of ATA to be specific for PMCA4 and that ATA may be a further experimental tool for elucidating the role of PMCA4.     

Circulating endothelin parallels arterial blood pressure during sleep in healthy subjects

OBJECTIVE: To characterize plasma endothelin 1 (ET-1) and arterial blood pressure (ABP) time courses during the first complete non-rapid eye movement (NREM)-REM sleep cycle in healthy subjects, together with plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP). METHODS: Heart rate (HR), intra-arterial blood pressure and sleep electroencephalographic activity were recorded continuously during the night in eight healthy 20-28-year-old males. Blood was sampled every 10 min during their first complete sleep cycle for simultaneous measurements of plasma ET-1, PRA and ANP. RESULTS: Circulating ET-1 demonstrated significant variations during the sleep cycle (p<0.0001) that paralleled those of ABP (p<0.05) and HR (p<0.005), with a minimum during NREM sleep and a maximum during REM sleep. ET-1 time course opposed that of PRA which increases during NREM sleep and decreases during REM sleep (p<0.0005). Plasma ANP did not demonstrate systematic variation in relation with the sleep cycle. CONCLUSION: Circulating ET-1, which parallels variations of ABP, may participate in ABP regulation during sleep in healthy subjects, in association with the renin-angiotensin system.     

NG-monomethyl-l-arginine (NMA) restores arterial blood pressure but reduces cardiac output in a canine model of endotoxic shock

Previous studies have suggested that NMA or similar inhibitors of nitric oxide synthesis from L-arginine reverses or prevents the hypotension associated with endotoxin administration. We wanted to determine if vascular and cardiac responses to NMA support the idea that inhibitors of nitric oxide synthesis might be useful in the treatment of septic shock. Pentobarbital-anesthetized beagle dogs were administered endotoxin for 2 hours at a dose of 250 ng/kg/min. This resulted in reductions in systemic vascular resistance (34% decrease) and mean arterial pressure (25% decrease). Administration of NMA (30 mg/kg, IV) caused large and sustained increases in mean arterial pressure and systemic vascular resistance, and a large decrease in cardiac output and femoral arterial blood flow. Although NMA restored arterial pressure, the large and sustained fall in cardiac output suggests that the cardiovascular action of NMA is detrimental to dogs treated with endotoxin.     

Dynamic interactions between arterial pressure and sympathetic nerve activity: role of arterial baroreceptors

The role of arterial baroreceptors in controlling arterial pressure (AP) variability through changes in sympathetic nerve activity was examined in conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured continuously during 1-h periods in freely behaving rats that had been subjected to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before study (n = 10 in each group). Fast Fourier transform analysis revealed that chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing the so-called Mayer waves, and induced an eightfold increase in MAP power without altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of rats, coherence between RSNA and MAP was maximal in the MF band and was usually weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP showed the characteristics of a second-order low-pass filter containing a fixed time delay ( approximately 0.5 s). These results indicate that arterial baroreceptors are not involved in production of respiratory-related oscillations of RSNA but play a major role in the genesis of synchronous oscillations of MAP and RSNA at the frequency of Mayer waves. The weak coupling between slow fluctuations of RSNA and MAP in sham-operated and SAD rats points to the interference of noise sources unrelated to RSNA affecting MAP and of noise sources unrelated to MAP affecting RSNA.