Effect of prolactin on blood pressure and cardiovascular responsiveness in the rat

The effects of chronic ovine PRL (oPRL) infusion on resting systolic blood pressure (BP), heart rate, and pressor responsiveness to acute administration of norepinephrine and angiotensin were studied in adult male Sprague-Dawley rats. oPRL was administered over 7 days, via osmotic pump implanted ip on Day 1, at rates of 0, 0.15, 0.30, 0.60, 1.20, and 4.80 micrograms/hr. Resting BP and heart rate were indirectly determined in conscious rats by tail cuff technique on Days 1, 4, and 7 following pump implantation. In addition, acute pressor responses to ia norepinephrine (4.3 micrograms) and angiotensin (1.25 micrograms) were directly measured via arterial cannula in halothane-anesthetized rats on Day 7 of oPRL administration. oPRL infusion did not alter resting BP or heart rate over the 7 days. However, oPRL increased the BP response to norepinephrine at infusion rates of 0.60 and 4.80 micrograms/hr (P less than 0.01 vs controls). Body weight increases during the study were also greater in groups receiving 0.15, 0.30, 0.60, and 4.80 micrograms oPRL/hr (P less than 0.05) than those in control animals. oPRL decreased pressor responses to angiotensin at infusion rates of 0.30 and 1.20 micrograms/hr (P less than 0.01). These data suggest that, although the vascular effects of oPRL may not be evident under resting conditions, oPRL enhances vascular reactivity to norepinephrine infusion and depresses vascular reactivity to angiotensin infusion. Furthermore, at oPRL infusion rates which affect pressor responses to norepinephrine, oPRL increases body weight gain. These findings support a role for PRL in cardiovascular regulation during conditions of altered sympathetic activity.     

Attenuation of psychosocial stress-induced hypertension by gamma-linolenic acid (GLA) administration in rats

This study investigated a model of psychosocial stress-induced hypertension in the rat, and examined effects of the prostaglandin E precursor, gamma-linolenic acid (GLA) on the development of hypertension during psychosocial stress. In the first study, male rats were housed four/cage for an acclimation period of 21 days, followed by a 14-day control period. An experimental group (N = 12) was then placed in isolation cages for 14 days, then regrouped for a 7-day recovery period. Controls (N = 12) remained group-housed. Eight animals per group were sacrificed after the experimental period, and four per group after recovery for organ weight analysis. Mean systolic blood pressure (BP) was similar between groups during the control period (126 +/- 2 and 125 +/- 2 mm Hg), but increased during isolation, reaching 140 +/- 2 mm Hg (P less than 0.001) by Day 14. During recovery BP returned to control levels. No changes in heart rate, heart weight/body weight or adrenal weight were seen. The second study utilized a protocol similar to that of the experimental group of the first study, minus the recovery period. On Day 1 of the control period 28-day osmotic pumps were implanted ip, releasing olive oil or GLA in olive oil. Four groups of rats (N = 8/group) received either (i) olive oil (controls), (ii) 0.018 mg GLA/hr, (iii) 0.040 mg GLA/hr, or (iv) 0.040 mg GLA/hr with no stress. Organ weights were obtained following stress in groups 1-3. Controls developed a sustained elevation in BP within 24 hr of isolation. Animals receiving 0.018 mg GLA/hr developed elevated BP upon isolation, but the BP was less than that of controls on Days 1 (P less than 0.05) and 14 (P less than 0.001) of isolation. Animals receiving 0.040 mg GLA/hr demonstrated a greatly attenuated rise in BP vs controls (P less than 0.001) on all isolation days. GLA in unstressed rats had no effect on BP. Heart rate, heart weight/body weight, and adrenal weight were unchanged in all groups. These data suggest that (i) isolation is a useful tool for investigating reversible psychosocial stress-induced hypertension, and (ii) GLA, while not affecting BP in unstressed animals, produces a dose-dependent attenuation of the BP response to chronic stress.     

Effects of highly purified eicosapentaenoic acid on vascular reactivity to angiotensin II and norepinephrine in the rabbit

There is disagreement about whether supplementation of the diet with fish oil, which is rich in eicosapentaenoic acid (EPA), lowers blood pressure. We gave highly purified EPA in a soft capsule (90% ethyl ester form of EPA; EPA-E), to female rabbits (100 mg/kg/day) for 4 weeks. Vascular response to vasoconstrictor agents was assessed serially by measuring the systolic blood pressure using a Grand-Rothschild capsule in the ear. There was no change in systolic blood pressure of rabbits treated with EPA-E, but rabbits given EPA-E for one week or longer were significantly less responsive to the pressor effects of angiotensin II than the controls. Responses to norepinephrine did not change. Rabbits given EPA-E for four weeks had significantly more EPA in the serum, but there were no differences in serum levels of triglycerides, total cholesterol, or high-density lipoprotein cholesterol. These results suggest that vascular responses to exogenous angiotensin II can be selectively depressed by short-term treatment with EPA-E in rabbits without changing systolic blood pressure.     

Cardiovascular and norepinephrine responses of men and women to two cold pressor tests.

Two types of cold pressor tests were used to study gender differences in cardiovascular and plasma catecholamine responses. Ten male and ten female, young, healthy Caucasian subjects participated. The tests consisted of (1) 5 degrees C air blown at 3.5-4 m/s onto part of the face for 4 min and (2) the open right hand immersed to the wrist in water at 5 degrees C for 4 min. Heart rate, blood pressure (BP), and venous plasma norepinephrine were collected before, during, and 5 min after the 4 min of cold exposures. Test order was decided by a Latin square design, and the subjects rested in a quiet room for 30 min between the two tests. All parameters demonstrated significant (p less than 0.01) increases from rest during the cold tests. Gender differences were significant (p less than 0.01) in diastolic and systolic BP in each test with the males having a greater response, but gender differences were not found in heart rate or norepinephrine concentration. The study demonstrated that gender differences exist in the blood pressure responses to local cold, but that the mechanisms involved do not include a parallel difference in heart rate or venous plasma norepinephrine concentration.     

Effects of angiotensin II on pressor responses to norepinephrine in humans

In previous studies in the conscious rabbit and in isolated artery preparations, low doses of angiotensin II synergistically amplified the pressor effects of the sympathetic neurotransmitter, norepinephrine (NE). To determine whether these observations could be replicated in humans, 9 normal adult male volunteers (mean age: 34) each were given 3 i.v. doses of NE (25, 50 and 100 micrograms.kg-1.min-1) during consecutive 10 min infusion periods. On a second study day, the procedure was repeated during infusion of angiotensin II in a subpressor dose (1.25 ng.kg-1.min-1). The angiotensin II didn't alter the BP responses to NE, but it attenuated the heart rate (HR) decreases associated with the NE infusions by 80% (P less than 0.05), 42% (P less than 0.05) and 42% (P less than 0.1). The two study days were then repeated following 2 weeks of oral treatment with the angiotensin converting enzyme inhibitor captopril (which, despite significantly decreasing baseline BP, also tended to decrease HR). In the presence of captopril, the pressor responses to the NE challenges were reduced by 50% (P less than 0.05), 33% (P less than 0.05) and 13% (P less than 0.1) compared with the pre-captopril responses. Thus, angiotensin II in subpressor doses appears to enhance NE pressor effects by attenuating the compensatory HR responses, whereas inhibition of endogenous angiotensin II mechanisms weakens the BP-raising actions of NE. These findings in humans are consistent with earlier observations that the renin-angiotensin system can directly amplify sympathetic pressor effects in two separate ways: by modifying baroreceptor sensitivity and by enhancing the actions of norepinephrine on vascular smooth muscle.     

Left ventricular catecholamines during acute myocardial infarction in the dog

To determine whether changes in left ventricular catecholamine content occur during the first 30 to 90 min of acute myocardial infarction, myocardial catecholamine (radioenzymatic assay) over the interval was studied in the dog. In nine pentobarbital-anesthetized opened-chest dogs without coronary ligation, myocardial catecholamine at 2.5 h after pentobarbital (i) consisted mainly of norepinephrine (87% total catecholamine), (ii) showed a base to apex gradient in norepinephrine (1.44 +/- 0.10 vs. 1.03 +/- 0.10 micrograms/g, p less than 0.05) and dopamine (0.20 +/- 0.03 vs. 0.12 +/- 0.02 micrograms/g, p less than 0.05) but not epinephrine (0.017 vs. 0.016 micrograms/g), and (iii) showed no difference in norepinephrine, dopamine, or epinephrine across basal, mid, and apical left ventricular transverse planes spanning the vascular territories of the two coronary arteries. In 18 pentobarbital-anesthetized dogs with coronary ligation, (i) norepinephrine, measured in 14 regions across the mid left ventricle after 90 min ischemia in four dogs, was less in the ischemic center of the occluded bed than normal myocardium (1.01 +/- 0.04 vs. 1.29 +/- 0.04 micrograms/g, p less than 0.05), and (ii) norepinephrine was unchanged in normal myocardium of 14 dogs at 30, 60, 90 min, and 48 h but decreased in ischemic myocardium by 31% at 60 min (0.89 +/- 0.10 vs. 1.29 +/- 0.08 micrograms/g, p less than 0.025) and 79% at 48 h (0.27 +/- 0.04 vs. 1.26 +/- 0.08 micrograms/g, p less than 0.001). Thus, norepinephrine depletion from ischemic but not normal myocardium is detectable by 60 min during acute myocardial infarction.     

Alterations in cardiovascular responsiveness and adrenoceptor binding during catecholamine infusion hypertension in rats.

Chronic continuous infusion of norepinephrine in rats causes alterations in biochemical and physiologic responses of the cardiovascular system and in cardiovascular adrenoceptor number. The response of cardiac and aortic ornithine decarboxylase (ODC) activity to stimulation by norepinephrine was decreased in rats receiving norepinephrine infusion. These responses are due to stimulation of beta- and alpha-adrenergic receptors, respectively. Additionally, there was reduced stimulation of aortic ODC activity by angiotensin II and vasopressin. The cardiac ODC response to angiotensin II was decreased, but the response to vasopressin was not affected. The decreased ODC response is accompanied by decreased pressor responses to the alpha-adrenergic agonist phenylephrine. Decreased numbers of alpha- and beta-adrenoceptor binding sites (as measured by the binding of [3H]prazosin and [125I]pindolol) might mediate, in part, the altered responses to adrenergic agonists. The decreased cardiovascular responsiveness measured in these animals after several days of norepinephrine infusion hypertension contrasts with the increased responses found in most other forms of hypertension. This provides a useful model in which to examine the consequences of prolonged adrenergic receptor stimulation.     

Diet‐induced Obesity Delays Cardiovascular Recovery from Stress in Spontaneously Hypertensive Rats

Objective: Blood pressure (BP) and heart rate (HR) responses to stress are significant predictors of cardiovascular morbidity and mortality. Because obesity is a major risk factor for cardiovascular disease, we examined whether diet‐induced obesity alters the BP and HR responses to stress and whether these alterations are associated with augmented cardiovascular morbidity in the rat. Research Methods and Procedures: Adult male spontaneously hypertensive rats were fed either a normal diet or high‐fat diet (HFD) for 12 weeks. At weeks 0 and 12, body weight was measured, and BP and HR were recorded by radiotelemetry throughout three consecutive day and night periods and in response to 30‐minute immobilization stress. At the end of the 12‐week intervention, the rats were sacrificed, and their organs and sera were collected. Results: With the intervention, HFD rats showed a significantly greater increase in body weight (as expected) and circulating leptin and free fatty acid levels compared with normal diet rats. In addition, they showed similar increases in BP and HR elevations during stress but significantly slower BP and HR decreases after stress. These HFD‐induced delays in stress recovery were associated with BP and HR elevations during the night (behaviorally active) period and with augmentations in cardiac mass. Discussion: The results of this study indicate that, in spontaneously hypertensive rats, dietary obesity delays cardiovascular recovery from stress, and, in parallel, it promotes the development of nocturnal hypertension as well as cardiac hypertrophy. This suggests that dietary obesity may significantly potentiate the impact of daily stressful experiences on the cardiovascular system.     

Effects of highly purified eicosapentaenoic acid on vascular reactivity to angiotensin II and norepinephrine in the rabbit

There is disagreement about whether supplementation of the diet with fish oil, which is rich in eicosapentaenoic acid (EPA), lowers blood pressure. We gave highly purified EPA in a soft capsule (90% ethyl ester form of EPA; EPA-E), to female rabbits (100 mg/kg/day) for 4 weeks. Vascular response to vasoconstrictor agents was assessed serially by measuring the systolic blood pressure using a Grand-Rothschild capsule in the ear. There was no change in systolic blood pressure of rabbits treated with EPA-E, but rabbits given EPA-E for one week or longer were significantly less respomsive to the pressor effects of angiotensin II than the controls. Responses to noripinephrine did not change. Rabbits given EPA-E for four weeks had significantly more EPA in the serum, but there were no differences in serum levels of triglycerides, total cholesterol, or high-density lipoprotein cholesterol. These results suggest that vascular responses to exogenous angiotensin II can be selectively depressed by short-term treatment with EPA-E in rabbits without changing systolic blood pressure.     

GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in rats

Background

Previous randomized controlled trials demonstrated a protective effect of renin angiotensin system blocking agents for the development of type-2 diabetes in patients with pre-diabetes. However, there are no real-world data available to illustrate the relevance for clinical practice.

Methods

Open, prospective, parallel group study comparing patients with an ACE inhibitor versus a diuretic based treatment. The principal aim was to document the first manifestation of type-2 diabetes in either group.

Results

A total of 2,011 patients were enrolled (mean age 69.1 ± 10.3 years; 51.6% female). 1,507 patients were available for the per-protocol analysis (1,029 ramipril, 478 diuretic group). New-onset diabetes was less frequent in the ramipril than in the diuretic group over 4 years. Differences were statistically different at a median duration of 3 years (24.4% vs 29.5%; p < 0.05). Both treatments were equally effective in reducing BP (14.7 ± 18.0/8.5 ± 8.2 mmHg and 12.7 ± 18.1/7.0 ± 8.3 mmHg) at the 4 year follow-up (p < 0.001 vs. baseline; p = n.s. between groups). In 38.6% and 39.7% of patients BP was below 130/80 mmHg (median time-to-target 3 months). There was a significant reduction of cardiovascular morbidity and mortality in favour of ramipril (p = 0.033). No significant differences were found for a change in HbA1c as well as for fasting blood glucose levels during follow-up. The rate of adverse events was higher in diuretic treated patients (SAE 15.4 vs. 12.4%; p < 0.05; AE 26.6 vs. 25.6%; p = n.s).

Conclusions

Ramipril treatment is preferable over diuretic based treatment regimens for the treatment of hypertension in pre-diabetic patients, because new-onset diabetes is delayed.     

Dietary n-3 PUFAs affect the blood pressure rise and cardiac impairments in a hyperinsulinemia rat model in vivo

The cardiovascular consequences of eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-specific intake were evaluated in vivo in a hyperinsulinemia (HI) model induced by dietary fructose intake. Wistar rats were fed a diet containing (or not for control) either EPA or DHA. The rise in blood pressure (BP), heart rate, and ECG were continuously monitored using an intra-abdominal telemetry system. The myocardial phospholipid fatty acid profile was significantly affected by DHA intake but less by EPA intake. The data indicated a reduced rise in BP in both DHA and EPA HI groups compared with controls. This result was confirmed by tail-cuff measurement after 5 wk [133.3 +/- 1.67 and 142.5 +/- 1.12 mmHg in n-3 polyunsaturated fatty acid (PUFA) and control groups, respectively], whereas n-3 PUFA did not affect BP in non-HI rats (116.3 +/- 3.33 mmHg). The heart rate was lower in the HI DHA group than in the other two dietary HI groups. Moreover, DHA induced a significantly shorter QT interval. It is concluded that the cardioactive component of fish oils is DHA through a mechanism that may involve the cardiac adrenergic system.     

Does long-term experimental antiorthostasis lead to cardiovascular deconditioning in the rat?

Microgravity or simulated microgravity induces acute and chronic cardiovascular responses, whose mechanism is pivotal for understanding of physiological adaptation and pathophysiological consequences. We investigated hemodynamic responses of conscious Wistar rats to 45? head-down tilt (HDT) for 7 days. Arterial blood pressure (BP) was recorded by telemetry. Heart rate (HR), spectral properties and the spontaneous baroreflex sensitivity (sBRS) were calculated. Head-up tilt (HUT) was applied for 2 h before and after HDT to assess the degree of any possible cardiovascular deconditioning. Horizontal control BP and HR were 112.5+/-2.8 mmHg and 344.7+/-10 bpm, respectively. HDT elicited an elevation in BP and HR by 8.3 % and 8.8 %, respectively, in less than 1 h. These elevations in BP and HR were maintained for 2 and 3 days, respectively, and then normalized. Heart rate variability was unchanged, while sBRS was permanently reduced from the beginning of HDT (1.01+/-0.08 vs. 0.74+/-0.05 ms/mmHg). HUT tests before and after HDT resulted in BP elevations (6.9 vs. 11.6 %) and sBRS reduction (0.44 vs. 0.37 ms/mmHg), respectively. The pressor response during the post-HDT HUT test was accompanied by tachycardia (13.7 %). In conclusion, chronic HDT does not lead to symptoms of cardiovascular deconditioning. However the depressed sBRS and tachycardic response seen during the post-HDT HUT test may indicate disturbances in cardiovascular control.     

Hemodynamic and sympathoadrenal responses to mental stress during nitric oxide synthesis inhibition

Cardiovascular and sympathoadrenal responses to a reproducible mental stress test were investigated in eight healthy young men before and during intravenous infusion of the nitric oxide (NO) synthesis inhibitor N-monomethyl-L-arginine (L-NMMA). Before L-NMMA, stress responses included significant increases in heart rate, mean arterial pressure, and cardiac output (CO) and decreases in systemic and forearm vascular resistance. Arterial plasma norepinephrine (NE) increased. At rest after 30 min of infusion of L-NMMA (0.3 mg.kg(-1).min(-1) iv), mean arterial pressure increased from 98 +/- 4 to 108 +/- 3 mmHg (P <0.001) because of an increase in systemic vascular resistance from 12.9 +/- 0.5 to 18.5 +/- 0.9 units (P <0.001). CO decreased from 7.7 +/- 0.4 to 5.9 +/- 0.3 l/min (P <0.01). Arterial plasma NE decreased from 2.08 +/- 0.16 to 1.47 +/- 0.14 nmol/l. Repeated mental stress during continued infusion of L-NMMA (0.15 mg.kg(-1).min(-1)) induced qualitatively similar cardiovascular responses, but there was a marked attenuation of the increase in mean arterial blood pressure, resulting in similar "steady-state" blood pressures during mental stress without and with NO blockade. Increases in heart rate and CO were attenuated, but stress-induced decreases in systemic and forearm vascular resistance were essentially unchanged. Arterial plasma NE increased less than during the first stress test. Thus the increased arterial tone at rest during L-NMMA infusion is compensated for by attenuated increases in blood pressure during mental stress, mainly through a markedly attenuated CO response and suppressed sympathetic nerve activity.     

Effects of CL 115,347, (+/-)-15-deoxy-16-hydroxy-16-vinyl-PGE2 methyl ester, on cardiovascular responses and plasma catecholamines in pithed stroke-prone spontaneously hypertensive rats during sympathetic stimulation

The effect of CL 115,347, a topically active antihypertensive PGE2 analog, and PGE2 on changes in blood pressure (BP), heart rate (HR) response and plasma epinephrine (E) and norepinephrine (NE) levels induced by stimulation of the sympathetic spinal cord outflow were studied in pithed stroke-prone spontaneously hypertensive rats (SHRSP). Surgical pithing significantly reduced plasma E but not NE levels suggesting that the sympathoadrenal medullary system differentially affects E and NE release. Sympathetic stimulation of the spinal cord of pithed SHRSP increased HR, BP, plasma E and NE levels. Topically applied CL 115,347 (0.001-0.2 mg/kg) dose-dependently decreased BP, while intravenously infused PGE2 (30 micrograms/kg/min) did not alter BP except for a brief initial drop. Topical application of CL 115,347 (0.1 mg/kg) also inhibited BP responses to sympathetic stimulation without effects on HR or plasma E or NE levels. Intravenous infusion of PGE2 (30 micrograms/kg/min) inhibited both BP and HR responses to spinal cord stimulation but did not alter plasma catecholamine levels. These studies in SHRSP suggest that CL 115,347 and PGE2 modulate cardiovascular responses mainly via postjunctional effects, but act differently on the cardiovascular elements, viz. CL 115,347 acts primarily on blood vessels while PGE2 acts on blood vessels and heart.     

Evaluation of circuit-training intensity for firefighters

Firefighters are required to perform a variety of strenuous occupational tasks that require high levels of both aerobic and anaerobic fitness. Thus, it is critical that firefighters train at an appropriate intensity to develop adequate levels of aerobic and anaerobic fitness. Circuit training is a unique training method that stresses both energy systems and therefore may be a viable training method to enhance firefighter preparedness. Thus, the purpose of this study was to compare the aerobic and anaerobic intensities of a circuit-based workout to physiological data previously reported on firefighters performing fire suppression and rescue tasks. Twenty career firefighters performed a workout that included 2 rotations of 12 exercises that stressed all major muscle groups. Heart rate was recorded at the completion of each exercise. Blood lactate was measured before and approximately 5 minutes after the workout. The workout heart rate and post-workout blood lactate responses were statistically compared to data reported on firefighters performing fire suppression and rescue tasks. The mean circuit-training heart rate was similar to previously reported heart rate responses from firefighters performing simulated smoke-diving tasks (79 ± 5 vs. 79 ± 6% maximum heart rate [HRmax], p = 0.741), but lower than previously reported heart rate responses from firefighters performing fire suppression tasks (79 ± 5 vs. 88 ± 6% HRmax, p < 0.001). The workout produced a similar peak blood lactate compared to that when performing firefighting tasks (12 ± 3 vs. 13 ± 3 mmol·L(-1), p = 0.084). In general, the circuit-based workout produced a lower cardiovascular stress but a similar anaerobic stress as compared to performing firefighting tasks. Therefore, firefighters should supplement low-intensity circuit-training programs with high-intensity cardiovascular and resistance training (e.g., ≥85% 1-repetition maximum) exercises to adequately prepare for the variable physical demands of firefighting.     

Dietary supplementation with 2-deoxy-D-glucose improves cardiovascular and neuroendocrine stress adaptation in rats

Dietary restriction and physical exercise can enhance stress resistance and reduce the risk of cardiovascular disease. We investigated the effects of dietary supplementation with 2-deoxy-d-glucose (2-DG), a glucose analog that limits glucose availability at the cellular level, on cardiovascular and neuroendocrine responses to stress in rats. Young adult male Sprague-Dawley rats were implanted with telemetry probes to monitor blood pressure (BP), heart rate, body temperature, and body movements. These variables were measured at designated times during a 6-mo period in rats fed control and 2-DG-supplemented (0.4% 2-DG, fed ad libitum on a schedule of 2 days on the diet and 1 day off the diet) diets during unperturbed conditions and during and after immobilization stress or cold-water swim stress. Rats fed the 2-DG diet exhibited significant reductions in resting BP, attenuated BP responses during stress, and accelerated recovery to baseline after stress. Plasma concentrations of ACTH and corticosterone were elevated under nonstress conditions in rats fed the 2-DG diet and exhibited differential responses to single (enhanced response) and multiple (reduced response) stress sessions compared with rats fed control rat chow ad libitum. The 2-DG diet improved glucose metabolism, as indicated by decreased concentrations of blood glucose and insulin under nonstress conditions, but glucose and insulin responses to stress were maintained. We conclude that improvements in some cardiovascular risk factors and stress adaptation in rats maintained on a 2-DG-supplemented diet are associated with reduced neuroendocrine responses to the stressors.     

Neurovascular responses to mental stress in prehypertensive humans

Neurovascular responses to mental stress have been linked to several cardiovascular diseases, including hypertension. Mean arterial pressure (MAP), muscle sympathetic nerve activity (MSNA), and forearm vascular responses to mental stress are well documented in normotensive (NT) subjects, but responses in prehypertensive (PHT) subjects remain unclear. We tested the hypothesis that PHT would elicit a more dramatic increase of MAP during mental stress via augmented MSNA and blunted forearm vascular conductance (FVC). We examined 17 PHT (systolic 120-139 and/or diastolic 80-89 mmHg; 22 ± 1 yr) and 18 NT (systolic < 120 and diastolic < 80 mmHg; 23 ± 2 yr) subjects. Heart rate, MAP, MSNA, FVC, and calf vascular conductance were measured during 5 min of baseline and 5 min of mental stress (mental arithmetic). Mental stress increased MAP and FVC in both groups, but the increases in MAP were augmented (Δ 10 ± 1 vs. Δ14 ± 1 mmHg; P < 0.05), and the increases in FVC were blunted (Δ95 ± 14 vs. Δ37 ± 8%; P < 0.001) in PHT subjects. Mental stress elicited similar increases in MSNA (Δ7 ± 2 vs. Δ6 ± 2 bursts/min), heart rate (Δ21 ± 3 vs. Δ18 ± 3 beats/min), and calf vascular conductance (Δ29 ± 10 vs. Δ19 ± 5%) in NT and PHT subjects, respectively. In conclusion, mental stress elicits an augmented pressor response in PHT subjects. This augmentation appears to be associated with altered forearm vascular, but not MSNA, responses to mental stress.     

Sex differences in social stress-induced pressor and behavioral responses in normotensive and prehypertensive rats

This study investigated sex differences in chronic social stress-induced pressor and behavioral responses in normotensive and prehypertensive rats. Adult Wistar and borderline hypertensive (BH) rats (offspring of Wistar dams and spontaneously hypertensive sires) of both sexes were exposed to crowding stress (200 cm2/rat, 5 rats/cage) for 6 weeks. Controls were kept 4 rats/cage (480 cm2/rat). Blood pressure (BP) and open field activity were determined before experiment and after 1, 3 and 6 weeks of stress. Basal BP of BH rats was higher than in Wistar (p < 0.001) in both males and females. Horizontal and vertical activity of BH males and females was elevated vs. Wistar (p < 0.01) and females in both phenotypes were more active than the respective males (p < 0.01). Crowding resulted in delayed between-session habituation and significant elevation of BP only in BH males (143 ± 2 vs. 134 ± 3 mmHg in controls after 6-week crowding). No changes of BP were observed in crowded females of both phenotypes regardless of their delayed between-session habituation. Thus chronic social stress produced by crowding seems to represent a significant risk factor for development of stress-related hypertension only in males with genetic predisposition to high blood pressure while females of both phenotypes responded to stress by impaired between-session habituation.     

Angiotensin II mediates hyperadrenergic activity evoked by sodium restriction in essential hypertension

We examined the possible involvement of angiotensin II in the modulation of circulating norepinephrine produced by acute sodium restriction in essential hypertensive patients (n = 18). Sodium restriction potentiated plasma level of norepinephrine in parallel with an increased plasma renin activity (r = 0.81, F = 31.2, p less than 0.05 given by the percent changes). An intravenous infusion of sarcosine-1, isoleucine-8 angiotensin II produced a significant fall in mean arterial pressure (-6 +/- 2 mmHg, p less than 0.05) in patients on sodium restriction but not before sodium restriction, while the infusion of the antagonist produced a greater decrease (p less than 0.05) in plasma norepinephrine with sodium restriction (-158 +/- 23 pg/ml, p less than 0.05) when compared to that obtained before sodium restriction (-91 +/- 11 pg/ml, p less than 0.05). A single oral administration of an angiotensin I converting enzyme inhibitor, captopril caused a greater fall (p less than 0.01) in mean arterial pressure after sodium restriction (-32 +/- 3 mmHg, p less than 0.05) compared to that given before (-21 +/- 3 mmHg, p less than 0.05). However, sodium restriction did not affect the magnitude of reflex increase in plasma norepinephrine to hypotension evoked by captopril (from +88 +/- 16 pg/ml to +87 +/- 17 pg/ml; p greater than 0.05). It can be interpreted that acute sodium depletion results in a substantial contribution of angiotensin II to the expression of hyperadrenergic activity.     

Effects of CL 115,347, (±)-15-deoxy-16-vinyl-PGE2 methyl ester, on cardiovascular responses and plasma catecholamines in pithed stroke-prone spontaneously hypertensive rats during sympathetic stimulation

The effect of CL 115,347, a topically active antihypertensive PGE₂ analog, and PGE₂ on changes in blood pressure (BP), heart rate (HR) response and plasma epinephrine (E) and norepinephrine (NE) levels induced by stimulation of the sympathetic spinal cord outflow were studied in pithed stroke-prone spontaneously hypertensive rats (SHRSP). Surgical pithing significantly reduced plasma E but not NE levels suggesting that the sympathoadrenal medullary system differentially affects E and NE release. Sympathetic stimulation of the spinal cord of pithed SHRSP increased HR, BP, plasma E and NE levels. Topically applied CL 115,347 (0.001–0.1 mg/kg) dose-dependently decreased BP, while intravenously infused PGE₂ (30 μg/kg/min) did not alter BP except for a brief initial drop. Topical application of CL 115,347 (0.1 mg/kg) also inhibited BP responses to sympathetic stimulation without effects on HR or plasma E or NE levels. Intravenous infusion of PGE₂ (30 μg/kg/min) inhibited both BP and HR responses to spinal cord stimulation but did not alter plasma catecholamine levels. These studies in SHRSP suggest that CL 115,347 and PGE₂ modulate cardiovascular responses mainly via postjunctional effects, but act differently on the cardiovascular elements, CL 115,347 acts primarily on blood vessels while PGE₂ acts on blood vessels and heart.