Effect of hypotension on the arterial system responsiveness

The correlation analysis revealed no correlation within the range 110 to 80 mm Hg further transforming into a direct (within the range lower than 80 mm Hg) dependence of the pressure responses to mesatone on the reduction of initial mean arterial pressure under orthostatic hypotension in anaesthetised rats. Under paraverine hypotension a reverse correlation within the range 110-80 mm Hg transforming into a direct dependence (within the range lower than 80 mm Hg) of the responses to mesatone were observed. The dependence of cardiac shifts to mesatone on the initial arterial pressure was not occurred. The mechanisms of dependence of the systemic vascular responses on initial tone of arterial vessels, are discussed.     

The combined effect of the cold pressor test and isometric exercise on heart rate and blood pressure

The purpose of this study was to determine if the cold pressor test during isometric knee extension [15% of maximal voluntary contraction (MVC)] could have an additive effect on cardiovascular responses. Systolic and diastolic blood pressures, heart rate and pressure rate product were measured in eight healthy male subjects. The subjects performed the cold pressor tests and isometric leg extensions singly and in combination. The increases of systolic and diastolic blood pressure during isometric exercise were of almost the same magnitude as those during the cold pressor test. The responses of arterial blood pressure, and heart rate to a combination of the cold pressor test and isometric knee extension were greater than for each test separately. It is suggested that this additional effect of cold immersion of one hand during isometric exercise may have been due to vasoconstriction effects in the contralateral unstressed limb. In summary, the circulatory effects of the local application of cold during static exercise at 15% MVC were additive.     

Increased dietary sodium alters neural control of blood pressure during intravenous ANG II infusion

Increased dietary sodium enhances both excitatory and inhibitory blood pressure responses to stimulation of the central sympathetic nervous system (SNS) centers. In addition, long-term (hours to days) administration of ANG II increases blood pressure by activation of the SNS. These studies investigated the effects of increased dietary sodium on SNS control of blood pressure during 0- to 24-h infusion of ANG II in conscious, male rats consuming either tap water or isotonic saline (Iso) for 2 to 3 wk. The SNS component (evaluated by ganglionic blockade with trimetaphan) of both control blood pressure and the pressor response to intravenous ANG II was reduced in Iso animals. Furthermore, although the pressor response to intravenous ANG II infusion was similar between groups, the baroreflex-induced bradycardia during the initial 6 h of ANG II infusion was significantly greater, whereas the tachycardia accompanying longer infusion periods was significantly attenuated in Iso animals. These data suggest that in normal rats increased dietary sodium enhances sympathoinhibitory responses during intravenous ANG II.     

Serum DBH in three forms of acute stress

We examined the changes in serum dopamine-β-hydroxylase (DBH) activity in men subjected to three forms of acute stress: cold pressor, sustained hand grip, and insulin-induced hypoglycemia. The responses to all three of these stresses are reported to be mediated by the sympathetic nervous system. In spite of striking increases in blood pressure induced by the cold pressor and sustained hand grip tests and the clinical and chemical evidence of hypoglycemia following insulin there was little alteration in serum DBH activity. A change in serum DBH level is not a good measure of acute alterations in sympathetic nervous system activity in men.     

Responses of the rat cardiovascular system to substance P,neurotensin and bombesin

The carotid arterial blood pressure and heart rate responses to intravenous injections of substance P, neurotensin and bombesin were compared in anaesthetized rats. In rats anaesthetized with urethane neurotensin produced only a fall in blood pressure but in rats anaesthetized with sodium thiobutabarbitone, the fall was preceded by a transient rise in blood pressure. The reason for the different responses to neurotensin with the two anaesthetics was not investigated. The hypotensive effect of neurotensin observed with both anaesthetics was abolished by mepyramine and therefore appeared to be mediated by action on H₁ receptors either of neurotensin directly or of histamine released. On the other hand, catecholamines might be implicated in the pressor response to neurotensin observed in rats anaesthetized with sodium thiobutabarbitone since it was reduced by phentolamine and hexamethonium. Low doses of substance P produced a depressor response which was not inhibited by the antagonists tested. At higher doses marked tachycardia occurred and the depressor response was less and was often followed by a pressor response. The tachycardia was abolished by propranolol but not by cervical cord section or by hexamethonium. Bombesin produced a pressor response which was unaffected by hexamethonium but was reversed to depressor by phentolamine. This depressor response to bombesin was abolished by propranolol. It was concluded that substance P produced a depressor response by action on its own specific receptors and tachycardia by catecholamine release whereas neurotensin and bombesin produced cardiovascular actions which were mediated entirely by amine release.     

Influence of OKY-1581 on responses to arachidonic acid in the feline pulmonary vascular bed

The effects of OKY-1581, a thromboxane synthesis inhibitor, on pulmonary vascular responses to arachidonic acid (AA) were investigated under baseline and elevated tone conditions in the intact chest cat. Under conditions of controlled blood flow at baseline tone, intralobar injections of AA increased lobar arterial pressure in a dose-related manner. These pressor responses were reduced by OKY-1581, and a small vasodilator response was unmasked. The administration of indomethacin to these same animals abolished all responses to AA. When baseline tone in the pulmonary vascular bed was elevated by infusion of U46619, intralobar injections of AA caused a biphasic change in lobar arterial pressure characterized by an initial increase followed by a secondary fall in pressure. Treatment with OKY-1581 attenuated the pressor component of the response and enhanced the depressor component of the response. All responses to AA at elevated tone were also blocked by indomethacin. Pressor responses to intralobar injections of U46619 were not altered by OKY-1581 or indomethacin and were similar under baseline and high pulmonary vascular tone conditions. The results of this study suggest that the pulmonary pressor response to AA in the cat is dependent in large part on the formation of TXA2 and also suggest that TXA2, PGI2, and vasoconstrictor prostaglandins (PGF2 alpha, PGD2, PGE2) are formed from AA in the cat lung.     

Effect of water deprivation on the centrally-mediated hypertensive response to clonidine in freely moving, normotensive rats

Effects of water deprivation on pressor responses to centrally and peripherally administered clonidine was investigated in freely moving, normotensive rats with chronic guide cannula and catheters implanted into the abdominal aorta via the femoral artery. In normal hydrated rats, intracerebroventricularly (i.c.v.) injected clonidine (10 and 20 micrograms) produced a dose-dependent and long-lasting rise in mean blood pressure (MBP) concomitant with a decrease in heart rate. However, a significant depressor response was not observed for up to 90 min. In 48 hr dehydrated rats, the pressor response to i.c.v. injected clonidine (10 and 20 micrograms) was significantly depressed and a depressor response appeared. Intravenously (i.v.) administered clonidine (25 micrograms/kg) in normal hydrated rats also produced a long-lasting pressor response following an initial rapid rise in MBP. The long-lasting pressor response to i.v. injected clonidine was abolished after water deprivation for 48 hr, whereas the initial rise in MBP was less affected. These results suggest that clonidine elicits centrally-mediated pressor response, which is influenced by body fluid volumes.     

Attenuated responses to sympathoexcitation in individuals with Down syndrome.

This study evaluated blood pressure and heart rate responses to exercise and nonexercise tasks as indexes of autonomic function in subjects with and without Down syndrome (DS). Twenty-four subjects (12 with and 12 without DS) completed maximal treadmill exercise, isometric handgrip (30% of maximum), and cold pressor tests, with heart rate and blood pressure measurements. Maximal heart rate and heart rate and blood pressure responses to the isometric handgrip and cold pressor tests were reduced in subjects with DS (P < 0.05). Both early (first 30 s) and late (last 30 s) responses were reduced. Obesity did not appear to influence the results, as both obese and normal-weight subjects with DS exhibited similar responses, and controlling for body mass index did not alter the results between controls and subjects with DS. Individuals with DS, without congenital heart disease, exhibit reduced heart rate and blood pressure responses to isometric handgrip exercise and cold pressor testing, consistent with autonomic dysfunction. Autonomic dysfunction may partially explain chronotropic incompetence observed during maximal treadmill exercise in individuals with DS.     

Markedly reduced blood pressure responsiveness in endotoxemic rats; reversal by neuropeptide Y

This study in conscious normotensive rats was performed to assess the effect of the vasoconstrictor peptide, neuropeptide Y (NPY), on blood pressure responsiveness to exogenous norepinephrine in endotoxaemia. NPY and endotoxin were infused at doses which had no effect on blood pressure, whether given alone or in combination. Endotoxin markedly reduced the pressor responses to bolus injections of norepinephrine. However, blood pressure responsiveness could be enhanced by infusing NPY simultaneously with the endotoxin. It is suggested that low dose NPY infusions may be clinically useful in reversing the reduced vascular responsiveness to pressor amines in shock.     

Cardiovascular and sympathetic nerve responses induced by intracerebroventricular injections of prostacyclin in rats

Intracerebroventricular (ICV) injections of prostacyclin (PGI2) produced biphasic blood pressure responses consisting of an initial hypotensive phase followed by a sustained pressor phase in awake rats. Heart rate increased following such injections in either awake or anesthetized rats. PGI2, 1 microgram, produced biphasic responses and, 10 micrograms, purely vasodepressor responses in anesthetized rats, but abdominal sympathetic nerve firing recorded was consistently increased. Hypophysectomy did not affect the hypotensive phase of the responses. These results indicate that the initial hypotension can not be explained by centrally-induced changes in sympathetic nerve activity or vasopressin release, but may be due to peripheral effects of PGI2 leaking from the injection site.     

The acute effects of capsaicin on the cardiovascular system

Arterial blood pressure and heart rate were recorded from male Wistar rats anaesthetized with urethane. Intravenous injection of capsaicin, 1 microgram, produced a reproducible triphasic effect on blood pressure, comprising an initial fall in blood pressure and heart rate, followed by a transient and then a sustained pressor response. The depressor response and bradycardia were abolished by vagal section. The transient pressor response was altered in shape by hexamethonium. Slow intravenous infusion of capsaicin, 50 micrograms over 12 min, produced only a sustained pressor response accompanied by tachycardia, which was resistant to hexamethonium but abolished by morphine and pithing. Responses to both 1 microgram injection and 50 micrograms infusion of capsaicin were unaffected by the SP antagonist, spantide, but were abolished by capsaicin pretreatment of the rats. Capsaicin induces complex effects on the cardiovascular system, the nature of which varies with the dose and speed of administration.     

Baroreflex modulation of muscle sympathetic nerve activity during cold pressor test in humans

The purpose of this project was to test the hypothesis that baroreceptor modulation of muscle sympathetic nerve activity (MSNA) and heart rate is altered during the cold pressor test. Ten subjects were exposed to a cold pressor test by immersing a hand in ice water for 3 min while arterial blood pressure, heart rate, and MSNA were recorded. During the second and third minute of the cold pressor test, blood pressure was lowered and then raised by intravenous bolus infusions of sodium nitroprusside and phenylephrine HCl, respectively. The slope of the relationship between MSNA and diastolic blood pressure was more negative (P < 0.005) during the cold pressor test (-244.9 +/- 26.3 units x beat(-1) x mmHg(-1)) when compared with control conditions (-138.8 +/- 18.6 units x beat(-1) x mmHg(-1)), whereas no significant change in the slope of the relationship between heart rate and systolic blood pressure was observed. These data suggest that baroreceptors remain capable of modulating MSNA and heart rate during a cold pressor test; however, the sensitivity of baroreflex modulation of MSNA is elevated without altering the sensitivity of baroreflex control of heart rate.     

Sleep states alter ventral medullary surface responses to blood pressure challenges

Ventral medullary surface (VMS) activity declines during rapid eye movement (REM) sleep, suggesting a potential for reduced VMS responsiveness to blood pressure challenges during that state. We measured VMS neural activity, assessed as changes in reflected 660-nm wavelength light, during pressor and depressor challenges within sleep/waking states in five adult, unrestrained, unanesthetized cats and in two control cats. Phenylephrine elevated blood pressure and elicited an initial VMS activity decline and a subsequent rise in VMS activity in all states, although the initial decline during quiet sleep occurred only in rostral placements. Phasic REM periods elicited a momentary recovery from the evoked activity rise, and arousals diminished the overall elevation in activity. A sodium nitroprusside depressor challenge increased VMS activity more in REM sleep than in quiet sleep, with the increase being even less in waking. Enhanced responses to depressor challenges during REM sleep suggest a loss of dampening of evoked activity during that state; state-related differential baroreflex sensitivity may result from sleep-waking changes in VMS responses to blood pressure challenges.     

Systemic site of action for pressor effect of angiotensin II injected into the fourth cerebral ventricle of rats?

Angiotensin II (ANG II) causes a systemic pressor effect when injected into the cerebral ventricles. In the rat fourth ventricle, the effective doses for the ANG II pressor effect are over 100 times larger than in the systemic circulation. Considering the discrepancy of doses, the possibility that ANG II may reach the systemic circulation and promote pressor effects, following injection into the fourth ventricle, was investigated. The effects on blood pressure of different vasoactive peptides that produce pressor responses when injected into the central nervous system were compared. Dose-response curves were obtained for intravenous or fourth cerebroventricular injections of ANG II, lysyl-vasopressin (LVP), bradykinin (BK), or endothelin-1 (ET-1). The ED50 ratios for intracerebroventricular/intraveneous injections were 110 for ANG II, 109 for LVP, 0.01 for BK, and approximately 0.4 for ET-1. In cross-circulation preparations, pressor responses occurred in the donor rat following injection into the fourth cerebral ventricle of the recipient animal, showing that effective doses of ANG II, administered to the fourth cerebral, reach the systemic circulation. The same results were obtained for the microinjection of 4 nmol of LVP into the fourth cerebral ventricle of recipient animals. High-performance reverse-phase liquid chromatography analyses of arterial blood showed that approximately 1% of the [125I]ANG II injected into the fourth cerebral ventricle may be recovered from the systemic circulation a few seconds after the microinjection. The systemic administration of the ANG II receptor antagonist losartan blocked the response to ANG II injected into the fourth ventricle whereas antagonist administration in the same ventricle did not. Angiotensin injections into the lateral ventricle produced pressor responses that were reduced by antagonist administration to the same ventricle but not by systemic administration of the antagonist. The data suggest that the pressor effect resulting from ANG II or LVP injections into the fourth cerebral ventricle may be due to the action of this peptide in the systemic circulation. On the other hand, the pressor effect due to ANG II microinjection into the lateral ventricle apparently results from the direct stimulation of central periventricular structures.     

Effects of prostaglandins E2, I2 and F2α, arachidonic acid and indomethacin on pressor responses to norepinephrine in conscious rats

The effects of prostaglandins E₂ (PGE₂), I₂ (PGI₂) and F₂α (PGF₂α), arachidonic acid and indomethacin on pressor responses to norepinephrine were examined in conscious rats. Intravenously infused PGE₂ (0.3, 1.25 μg/kg/min), PGI₂ (50, 100 ng/kg/min), PGF₂α (1.8, 5.4 μg/kg/min) and arachidonic acid (0.7, 1.4 mg/kg/min) did not change the basal blood pressure. Both PGE₂ and PGI₂ significantly attenuated pressor responses to norepinephrine, whereas PGF₂α significantly potentiated them. Arachidonic acid, a precursor of the prostaglandins (PGs), significantly attenuated pressor responses to norepinephrine. Since the attenuating effect of arachidonic acid was completely abolished by the pretreatment with indomethacin (5 mg/kg), arachidonic acid is thought to exert an effect through its conversion to PGs. On the contrary, intravenously injected indomethacin (0.2–5.0 mg/kg) facilitated pressor responses to norepinephrine in a dose-related manner without any direct effect on the basal blood pressure. These results suggest that endogenous PGs may participate in the regulation of blood pressure by modulating pressor responses to norepinephrine in conscious rats.     

Infusions of chemicals into the brain and the development of sustained elevations of blood pressure in the rat

Osmotic minipumps were used to infuse carbachol chloride (1.23 μg/hr), echothiophate iodide (0.5 μg/hr), histamine dihydrochloride (10 μg/hr), prostaglandin E₂ (1.0 μg/hr) and thyrotropin-releasing hormone (0.5 and 5.0 μg/hr) solutions into the cerebral ventricles of unanesthetized rats and blood pressure was measured by the tail-cuff method. Histamine dihydrochloride, prostaglandin E₂ and thyrotropin-releasing hormone produced an initial rise in blood pressure, but were not effective in producing sustained elevations in blood pressure. Carbachol infusions elevated blood pressure throughout the 7-day infusion period when results were compared to saline-infused animals. Infusions of echothiophate iodide, an anticholinesterase agent, produced an initial rise in blood pressure but these pressor effects were not sustained. In animals infused with echothiophate for 7 days, the pressor response to a challenge dose of echothiophate was diminished.     

Pressor and tachycardic responses to intravenous substance P in anesthetized rats

Intravenous injection of 3–33 nmol/kg of substance P (SP) caused pressor and tachycardic responses in anesthetized rats. The responses were not blocked by a ganglion nicotinic receptor antagonist or by pithing. Pretreatment with reserpine blocked both responses. β-Adrenoceptor blockade attenuated only the tachycardic response, and -adrenoceptor blockade attenuated only the pressor response. These findings indicated that the effects of SP to increase blood pressure and heart rate are due to sympathetic ganglion stimulation. Studies with adrenalectomized rats showed that stimulation of the adrenals by SP contributes to both responses but makes a greater contribution to the tachycardic response. These observations raise the possibility that the tachykinin innervation of sympathetic ganglia and the adrenal medulla may be involved in the local regulation of blood pressure and heart rate.     

Similar poststimulatory pressor responses with different mechanisms in response to excitation of the locus coeruleus before and after acute adrenalectomy

Electrical stimulation of the locus coeruleus in anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in blood pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response, which was accompanied by an increase in plasma noradrenaline and adrenaline levels, was stable and could be easily reproduced over time. Sympathectomy by administration of guanethidine selectively abolished the primary pressor response. beta-Adrenergic blockade by intravenous administration of sotalol enhanced the secondary pressor response without affecting the primary component. Adrenal demedullation performed 24-48 h before the experiments selectively prevented the secondary pressor component. In contrast, acute adrenalectomy carried out during the experiment to impair the adrenomedullary secretions eliminated the secondary pressor response to stimulation of the locus coeruleus only in sympathectomized or in sotalol-treated rats but not in intact rats in which the response persisted. The latter, however, could be abolished by the administration of either guanethidine or sotalol, and it disappeared following repeated stimulation of the locus coeruleus. The study demonstrates that similar poststimulatory pressor responses with different underlying mechanisms can be elicited on excitation of the locus coeruleus before and after acute adrenalectomy in the rat. The results also suggest that intraneuronal adrenaline may be involved in the response evoked in acutely adrenalectomized animals.     

Effect of atrial natriuretic factor on central angiotensin II-induced responses in rats

The effect of intracerebroventricular (ICV) injection of atrial natriuretic factor (ANF) on drinking and pressor responses induced by centrally administered angiotensin II (AII) was examined in the rat. The ICV injection of ANF attenuated water intake induced by AII or 48-hr water deprivation. In contrast, ANF did not affect AII-induced pressor responses. The ICV injection of ANF did not cause recognizable change in blood pressure in spontaneously hypertensive rats or Wistar-Kyoto rats. These results suggested that ANF in the brain is involved in the central control of water intake. Brain ANF may be considered as a selective antagonist of the dipsogenic effect of AII but not its pressor effect.     

Estrogen attenuates the cardiovascular and ventilatory responses to central command in cats.

Static exercise is well known to increase heart rate, arterial blood pressure, and ventilation. These increases appear to be less in women than in men, a difference that has been attributed to an effect of estrogen on neuronal function. In decerebrate male cats, we examined the effect of estrogen (17beta-estradiol; 0.001, 0.01, 0.1, and 1.0 microg/kg iv) on the cardiovascular and ventilatory responses to central command and the exercise pressor reflex, the two neural mechanisms responsible for evoking the autonomic and ventilatory responses to exercise. We found that 17beta-estradiol, in each of the three doses tested, attenuated the pressor, cardioaccelerator, and phrenic nerve responses to electrical stimulation of the mesencephalic locomotor region (i.e., central command). In contrast, none of the doses of 17beta-estradiol had any effect on the pressor, cardioaccelerator, and ventilatory responses to static contraction or stretch of the triceps surae muscles. We conclude that, in decerebrate male cats, estrogen injected intravenously attenuates cardiovascular and ventilatory responses to central command but has no effect on responses to the exercise pressor reflex.