Effects of acute exercise and prolonged exercise training on blood pressure, vasopressin and plasma renin activity in spontaneously hypertensive rats

The purpose of this study was to investigate the effect of swimming training on systolic blood pressure (BPs), plasma and brain vasopressin (AVP), and plasma renin activity (PRA) in spontaneously hypertensive rats (SHR) during rest and after exercise. Resting and postexercise heart rate, as well as blood parameters such as packed cell volume (PCV), haemoglobin concentration (Hb), plasma sodium and potassium concentrations ([Na+], [K+]) osmolality and proteins were also studied. Hypophyseal AVP had reduced significantly after exercise in the SHR, whereas PRA had increased significantly in the Wistar-Kyoto (WKY) strain used as normotensive controls. Plasma AVP concentration increased in both strains. By the end of the experiment, training had reduced body mass and BPs by only 10% and 6%, respectively. Maximal oxygen uptake was increased 10% and plasma osmolality 2% by training. The postexercise elevation of heart rate was not significantly attenuated by training. A statistically significant reduction in postexercise plasma osmolality (10%) and [Na+] (4%) was observed. These results suggested that swimming training reduced BPs. Plasma and brain AVP played a small role in the hypertensive process of SHR in basal conditions because changes in AVP contents did not correlate with those of BPs. Moreover, there were no differences between SHR and WKY in plasma, hypophyseal and hypothalamic AVP content in these basal conditions. Finally, during moderate exercise a haemodilution probably occurred with an increase of plasma protein content. This was confirmed by the exercise-induced increase of plasma AVP and the reduction of hypophyseal AVP content, suggesting a release of this hormone, which probably contributed to the water retention and haemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of the adenosine A1 receptor on blood pressure regulation and renin release

The present study was performed to investigate the role of adenosine A1 receptors in regulating blood pressure in conscious mice. Adenosine A1-receptor knockout (A1R-/-) mice and their wild-type (A1R+/+) littermates were placed on standardized normal-salt (NS), high-salt (HS), or salt-deficient (SD) diets for a minimum of 10 days before telemetric blood pressure and urinary excretion measurements in metabolic cages. On the NS diet, daytime and nighttime mean arterial blood pressure (MAP) was 7-10 mmHg higher in A1R-/- than in A1R+/+ mice. HS diet did not affect the MAP in A1R-/- mice, but the daytime and nighttime MAP of the A1R+/+ mice increased by approximately 10 mmHg, to the same level as that in the A1R-/-. On the SD diet, day- and nighttime MAP decreased by approximately 6 mmHg in both A1R-/- and A1R+/+ mice, although the MAP remained higher in A1R-/- than in A1R+/+ mice. Although plasma renin levels decreased with increased salt intake in both genotypes, the A1R-/- mice had an approximately twofold higher plasma renin concentration on all diets compared with A1R+/+ mice. Sodium excretion was elevated in the A1R-/- compared with the A1R+/+ mice on the NS diet. There was no difference in sodium excretion between the two genotypes on the HS diet. Even on the SD diet, A1R-/- mice had an increased sodium excretion compared with A1R+/+ mice. An abolished tubuloglomerular feedback response and reduced tubular reabsorption can account for the elevated salt excretion found in A1R-/- animals. The elevated plasma renin concentrations found in the A1R-/- mice could also result in increased blood pressure. Our results confirm that adenosine, acting through the adenosine A1 receptor, plays an important role in regulating blood pressure, renin release, and sodium excretion.     

Normal blood pressure and plasma renin activity in mice lacking the renin-binding protein, a cellular renin inhibitor

In renal extracts, some renin is present as "high molecular weight renin," a heterodimeric complex of renin with the 46-kDa renin-binding protein (RnBP), also known as N-acyl-D-glucosamine 2-epimerase. Because RnBP specifically inhibits renin activity, the protein was proposed to play an important role in the regulation of the renin-angiotensin system (RAS). Using gene targeting, we have generated mice lacking RnBP and tested this hypothesis in vivo. In particular, we analyzed biosynthesis, secretion, and activity of renin and other components of the RAS in mice lacking RnBP. Despite extensive investigations, we were unable to detect any major effects of RnBP deficiency on the plasma and renal RAS or on blood pressure regulation. Contrary to previous hypotheses, we conclude that RnBP does not play a significant role in the regulation of renin activity in plasma or kidney. However, RnBP knockout mice excrete an abnormal pattern of carbohydrates in the urine, indicating a role of the protein in renal carbohydrate metabolism.     

Effects of angiotensin II on arterial pressure, renin and aldosterone during exercise

To evaluate the effect of isotonic exercise on the response to angiotensin II, angiotensin II in saline solution was infused intravenously (7.5 ng X kg-1 X min-1) in seven normal sodium replete male volunteers before, during and after a graded uninterrupted exercise test on the bicycle ergometer until exhaustion. The subjects performed a similar exercise test on another day under randomized conditions when saline solution only was infused. At rest in recumbency angiotensin II infusion increased plasma angiotensin II from 17 to 162 pg X ml-1 (P less than 0.001). When the tests with and without angiotensin II are compared, the difference in plasma angiotensin II throughout the experiment ranged from 86 to 145 pg X ml-1. The difference in mean intra-arterial pressure averaged 17 mmHg at recumbent rest, 12 mmHg in the sitting position, 9 mmHg at 10% of peak work rate and declined progressively throughout the exercise test to become non-significant at the higher levels of activity. Plasma renin activity rose with increasing levels of activity but angiotensin II significantly reduced the increase. Plasma aldosterone, only measured at rest and at peak exercise, was higher during angiotensin II infusion; the difference in plasma aldosterone was significant at rest, but not at peak exercise. In conclusion, the exercise-induced elevation of angiotensin II does not appear to be an important factor in the increase of blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dissociated response of aldosterone from plasma renin activity during prolonged exercise under hypoxia

6 healthy male subjects on a fixed salt-diet performed 1 hour ergocycle exercise at 65% of VO2 max in normoxic (N) and hypoxic (H) conditions. Blood samples were taken at intervals for estimations of plasma aldosterone (PAC), angiotensin converting enzyme (ACE), adrenocorticotrophic hormone (ACTH) and catecholamine concentrations. Plasma volume reductions with exercise were similar in N (4.3 +/- 1%) and H (4.0 +/- 1%). PRA response to exercise was increased by hypoxia while PAC and plasma catecholamine rose to a similar extent in both conditions. Increases in ACTH concentration occurred at the end of exercise but no difference was found between high and low altitudes. Plasma ACE remained unchanged throughout exercise in either condition. These results indicate that hypoxemia interferes with PRA-mediated aldosterone secretion. The variations in plasma ACTH levels during exercise in hypoxia do not appear responsible for this interference.     

Circadian variations in plasma renin activity, catecholamines and aldosterone during exercise in women

Four women were studied at 0400 h and 1600 h to determine if their hormonal and hemodynamic responses to exercise varied with the circadian cycle. Esophageal temperature was measured during rest and exercise (60% peak VO2; 30 min) in a warm room (Ta = 35 degrees C; PH2O = 1.7 kPa). Venous blood samples were drawn during rest and exercise and hemoglobin concentration (Hb), hematocrit (Hct), plasma osmolality (Posm), plasma protein concentration (Pp), colloid osmotic pressure (COP), plasma renin activity (PRA), cortisol, aldosterone, norepinephrine (NE) and epinephrine (E) were determined. Changes in plasma volume (PV) were estimated from changes in Hb and Hct. The relative hemoconcentration (-11.2%) was similar at 0400 h and 1600 h, but the absolute PV was smaller at 1600 h than at 0400 h (p = 0.03). The responses of Posm, Pp and COP to exercise were unaffected by time of day. Although PRA was not different at the two times of day, PRA was 244% greater during exercise at 1600 h, but only 103% greater during exercise at 0400 h. The normal circadian rhythms in plasma aldosterone (p = 0.043) and plasma cortisol (p = 0.004) were observed. Plasma aldosterone was 57% greater during exercise, while plasma cortisol did not change. The change in E and NE was greater at 0400 h, but this was due to the lower resting values of the catecholamines at 0400 h. These data indicate that time of day generally did not affect the hormonal or hemodynamic responses to exercise, with the exception that PRA was markedly higher during exercise at 1600 h compared to 0400 h.     

Influence of hydrostatic pressure gradients on regulation of plasma volume after exercise

The impact of posture on the immediate recoveryof intravascular fluid and protein after intense exercise wasdetermined in 14 volunteers. Forces which govern fluid and proteinmovement in muscle interstitial fluid pressure(P_ISF), interstitial colloid osmotic pressure (COP_i), andplasma colloid osmotic pressure(COP_p) were measured before andafter exercise in the supine or upright position. During exercise,plasma volume (PV) decreased by 5.7 ± 0.7 and 7.0 ± 0.5 ml/kgbody weight in the supine and upright posture, respectively. Duringrecovery, PV returned to its baseline value within 30 min regardless ofposture. PV fell below this level by 60 and 120 min in the supine andupright posture, respectively (P < 0.05). Maintenance of PV in the upright position was associated with adecrease in systolic blood pressure, an increase inCOP_p (from 25 ± 1 to 27 ± 1 mmHg; P < 0.05), and an increasein P_ISF (from 5 ± 1 to 6 ± 2 mmHg), whereas COP_i wasunchanged. Increased P_ISFindicates that the hydrostatic pressure gradient favors fluid movementinto the vascular space. However, retention of the recaptured fluid inthe plasma is promoted only in the upright posture because of increasedCOP_p.

     

The effect of naloxone on blood pressure, heart rate, plasma catecholamines, renin activity and aldosterone following exercise in healthy males

There is evidence that endogenous opioids are involved in blood pressure regulation. In the present study the effect of naloxone on the cardiovascular, sympathoadrenomedullary and renin-aldosterone response to physical exercise was investigated in 8 healthy males. Each subject performed a submaximal work test twice, i.e. with and without naloxone. The test consisted of ergometer bicycling for 10 minutes on 50% of the maximal working capacity (MWC), immediately followed by 10 min on 80% of MWC. Ten minutes before exercise the subjects received in a single blind randomized order a bolus dose of naloxone (100 micrograms/kg) or a corresponding volume of the preservatives of the naloxone preparation (control) followed by a slow infusion of naloxone (50 micrograms/kg/h) or preservatives, respectively. Naloxone was without effect on the exercise-induced changes in systolic blood pressure, heart rate, plasma noradrenaline, renin activity and aldosterone, but the adrenaline response increased markedly. The present results indicate that opioid receptors are involved in the plasma adrenaline response to submaximal exercise, but not in the regulation of systolic blood pressure, heart rate, plasma noradrenaline, renin activity and plasma aldosterone.     

Beta-adrenoreceptor blockade in the conscious rabbit: effects on plasma renin activity and blood pressure.

The administration of a single dose of dl-propranolol, 1 mg/kg i.v., in the conscious unstimulated rabbit produced effective beta-adrenoreceptor blockade (inhibition of isoprenaline tachycardia) for 150 min. During this period there was a positive correlation between plasma concentrations of propranolol and the degree of beta-blockade observed. In a further group of animals treated with propranolol, plasma renin activity (PRA) fell to 50% of control (P < 0.001) within 60 min, the rate of change of PRA also correlating with plasma propranolol levels. Similarly, there were reductions in mean blood pressure (P < 0.025) and heart rate (P < 0.025). Statistical relationships between the fall in blood pressure and either pre-treatment PRA or the change in PRA were consistent with the hypothesis that the hypotensive effect of propranolol was dependent upon its suppression of renin release. However, an alternative possibility that the fall in blood pressure was due to an acute reduction in cardiac output could not be excluded.     

Effect of somatostatin on plasma renin activity and blood pressure in patients with essential hypertension

The effects of somatostatin on plasma renin activity (PRA) and blood pressure were evaluated in patients with essential hypertension (EH) and in normotensive subjects. All subjects examined were hospitalized and placed on a diet containing 7-8 g/day sodium chloride and received an intravenous infusion of somatostatin (500 microgram/20 ml of saline, for 60 min) in the basal condition. During somatostatin infusion, the mean blood pressure (MBP) remained unaffected in all patients with EH and the normotensive subjects, while the PRA decreased slightly in the EH group. When the patients with EH were classified according to their renin levels (low, normal and high), parallel significant decreases in MBP and PRA were found only in the high renin group during the somatostatin infusion. No significant change in MBP and PRA was observed in the other groups including the normotensive subjects. To assess the activity of synthetic somatostatin, the plasma levels of growth hormone (GH) and cyclic AMP were measured. These levels were lowered significantly during the infusion and the GH levels showed a rebound 15 min after cessation of the infusion. The cyclic AMP returned to the basal levels, but no rebound was observed. The above data indicate that the fall in blood pressure in the high renin group in the basal condition was probably due in part to reduced renin release by somatostatin, and the maintenance of high blood pressure especially in high renin EH.     

Effects of water intake on variations of plasma renin activity (PRA) and blood aldosterone during physical exercise in man]

In man, increase of renin and aldosterone levels in sera resulting from a brief and heavy muscular exercise on bicyle ergometer is notably reduced but not abolished by massive hydration.     

Increases in intramuscular pressure raise arterial blood pressure during dynamic exercise.

This investigation was designed to determine the role of intramuscular pressure-sensitive mechanoreceptors and chemically sensitive metaboreceptors in affecting the blood pressure response to dynamic exercise in humans. Sixteen subjects performed incremental (20 W/min) cycle exercise to fatigue under four conditions: control, exercise with thigh cuff occlusion of 90 Torr (Cuff occlusion), exercise with lower body positive pressure (LBPP) of 45 Torr, and a combination of thigh cuff occlusion and LBPP (combination). Indexes of central command (heart rate, oxygen uptake, ratings of perceived exertion, and electromyographic activity), cardiac output, stroke volume, and total peripheral resistance were not significantly different between the four conditions. Mechanical stimulation during LBPP and combination conditions resulted in significant elevations in intramuscular pressure and mean arterial pressure from control at rest and throughout the incremental exercise protocol (P < 0.05). Conversely, there existed no significant changes in mean arterial pressure when the metaboreflex was stimulated by cuff occlusion. These findings suggest that under normal conditions the mechanoreflex is tonically active and is the primary mediator of exercise pressor reflex-induced alterations in arterial blood pressure during submaximal dynamic exercise in humans.     

Effect of blood volume on plasma volume shift during exercise

To assess the relationship between blood volume (BV) and the reduction in plasma volume (PV) during exercise in individual variations, we measured BV and changes in PV in thirteen male volunteers during treadmill exercise until exhaustion. The lactate threshold (LT), as a predictor of aerobic exercise capacity, was calculated from the exercise intensity at the point of plasma lactate concentration buildup to 4 mmol. The relationship of peak VO₂ with BV indicated a significant positive correlation. The strong positive relation between the shifts in PV and total PV, and resulted in a maintenance of the circulating BV.     

The rat renin gene: assignment to chromosome 13 and linkage to the regulation of blood pressure.

It has recently been suggested that in the rat, sequence variation in the renin gene or closely linked genes may have the capacity to affect blood pressure and contribute to the pathogenesis of hypertension. To map the chromosomal location of the rat renin gene and to investigate its relationship to the inheritance of increased blood pressure, we studied a panel of rat x mouse somatic cell hybrids and a large set of recombinant inbred (RI) strains derived from spontaneously hypertensive rats (SHR) and normotensive Brown-Norway (BN) rats. We have found that in the rat, the renin gene is located on chromosome 13 and that it belongs to a conserved synteny group located on chromosome 1 in man and mouse. We have also found the median blood pressure of the RI strains that inherited the renin allele of the SHR to be greater than that of the RI strains that inherited the renin allele of the normotensive BN rat. These findings, together with the results of previous studies, suggest that in the rat, sequence variation in the renin gene, or in genes linked to the renin locus on chromosome 13, may have the capacity to affect blood pressure.     

O2 uptake and blood pressure regulation at the onset of exercise: interaction of circadian rhythm and priming exercise

Circadian rhythm has an influence on several physiological functions that contribute to athletic performance. We tested the hypothesis that circadian rhythm would affect blood pressure (BP) responses but not O(2) uptake (Vo(2)) kinetics during the transitions to moderate and heavy cycling exercises. Nine male athletes (peak Vo(2): 60.5 ± 3.2 ml·kg(-1)·min(-1)) performed multiple rides of two different cycling protocols involving sequences of 6-min bouts at moderate or heavy intensities interspersed by a 20-W baseline in the morning (7 AM) and evening (5 PM). Breath-by-breath Vo(2) and beat-by-beat BP estimated by finger cuff plethysmography were measured simultaneously throughout the protocols. Circadian rhythm did not affect Vo(2) onset kinetics determined from the phase II time constant (τ(2)) during either moderate or heavy exercise bouts with no prior priming exercise (τ(2) moderate exercise: morning 22.5 ± 4.6 s vs. evening 22.2 ± 4.6 s and τ(2) heavy exercise: morning 26.0 ± 2.7 s vs. evening 26.2 ± 2.6 s, P > 0.05). Priming exercise induced the same robust acceleration in Vo(2) kinetics during subsequent moderate and heavy exercise in the morning and evening. A novel finding was an overshoot in BP (estimated from finger cuff plethysmography) in the first minutes of each moderate and heavy exercise bout. After the initial overshoot, BP declined in association with increased skin blood flow between the third and sixth minute of the exercise bout. Priming exercise showed a greater effect in modulating the BP responses in the evening. These findings suggest that circadian rhythm interacts with priming exercise to lower BP during exercise after an initial overshoot with a greater influence in the evening associated with increased skin blood flow.     

Effect of deoxycorticosterone acetate and 16beta-hydroxy-dehydroepiandrosterone on blood pressure and plasma renin activity of rats.

Intact female Sprague-Dawley rats were given daily injections of either 3.125 mg of deoxycorticosterone or 5.0 mg of 16beta-hydroxy-dehydroepiandrosterone, calculated from the activities reported for each to be equivalent mineralocorticoid dosages. The former caused hypertension, cardiorenal enlargement, increased urine output and depressed PRA. Treatment with 16beta-OH-DHEA had no such effect, raising questions regarding its classification as a mineralocorticoid.