Blood pressure responses of conscious rats to intravenous administration of enkephalin derivatives (D-ala methionine and leucine enkephalinamide, and methionine and leucine enkephalinamide)

The present study was designed to determine the blood pressure (BP) responses of conscious rats given intravenous (IV) injections of enkephalin derivatives (D-ala²-methionine enkephalinamide, DAMEA; D-ala²-leucine enkephalinamide, DALEA; methionine enkephalinamide, MEA; leucine enkephalinamide, LEA) and the receptor mechanisms mediating the resultant change in BP. IV injection of 1.6–16.0 nmoles of DAMEA or DALEA caused a transient but potent decrease in mean arterial pressure (MAP) and mean heart rate (MHR). LEA and MEA (16.0 nmoles) given IV produced slight pressor responses, which were not associated with concomitant tachycardia whereas 48 nmoles of MEA elicited a hypotensive effect accompanied by a fall in MHR. Pretreatment studies whereby various receptor antagonists (naloxone, diprenorphine, phentolamine, D-L-propranolol or atropine) were given IV 5 min before subsequent IV administration of DAMEA, DALEA, MEA or LEA (16 nmoles) showed that naloxone, diprenorphine and atropine blocked the depressor and bradycardic effects of DALEA and DAMEA. Naloxone and phentolamine suppressed the pressor reponse of both MEA and LEA (16.0 nmoles) while diprenorphine blocked the rise in MAP to only MEA. The results show that DAMEA and DALEA mediate their depressor actions in conscious rats via a negative chronotropic effect through an interaction of muscarinic cholinergic receptors on the myocardium. It is suggested that the pressor response of MEA and LEA may be produced via an -receptor mediated effect on the peripheral vasculature to cause vasoconstriction.     

Opiate and alpha receptor antagonists block the pressor responses of conscious rats given intravenous dynorphin

Conscious, unrestrained rats were used to determine the hemodynamic (blood pressure and heart rate) responses following intravenous (IV) injection of dynorphin A(1-13) and the possible receptor mechanisms mediating those changes. Male Sprague-Dawley rats (300 g) were given IV bolus injections (via femoral venous catheter) of 6.0 to 600 nmoles/kg of dynorphin A(1-13), 8.0 nmoles/kg of norepinephrine HCl (NE), 14.3 pmoles/kg of angiotensin II or a vehicle control solution. Blood pressure (BP) and heart rate (HR) were monitored via femoral arterial catheter (into abdominal aorta) over 90 sec postpeptide or -amine administration before and 10 min after IV injection of 4.2 mumoles/kg of naloxone HCl (opiate antagonist), yohimbine HCl (alpha 2 receptor antagonist) or prazosin HCl (alpha 1 receptor antagonist). Dynorphin A(1-13) caused a transient but dose-related rise in mean arterial pressure (MAP) whereas mean pulse pressures (MPP) and mean heart rates (MHR) concomitantly fell, from preinjection control values in a dose-dependent fashion. Pretreatment with naloxone blocked the pressor response of only a subsequent injection with 20 nmoles/kg but not 60 nmoles/kg of dynorphin A or NE (8.0 nmoles/kg). Pretreatment with yohimbine suppressed the marked pressor responses of subsequent NE or Dyn A (60 nmoles/kg) administration whereas prazosin antagonized the rise in MAP of only the lower doses of dynorphin as well as NE. The suppression of the pressor responses of dynorphin by opiate or alpha receptor antagonists were not caused by tachyphylaxis for repeated injections of 6.0 or 60 nmoles/kg of dynorphin caused the same rise in MAP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pressor, tachycardic and feeding responses in conscious rats following i.c.v. administration of dynorphin. Central blockade by opiate and alpha 1-receptor antagonists

Experiments were designed to determine the hemodynamic responses of conscious, unrestrained rats given intracerebroventricular (i.c.v.) injections of dynorphin A-(1-13) and the possible central receptor mechanisms mediating those changes. Male Sprague-Dawley rats (300 gb. wt.) received i.c.v. injections (by gravity flow in a total volume of 3 or 5 microliter) of control solutions of sterile saline (SS) or dimethylsulfoxide (DMSO) or 1.5, 3.0 or 6.1 nmol of dynorphin A-(1-13). Blood pressure and heart rate changes were monitored over 2 h after administration; as well, feeding activity was visually assessed and scored over this period. Other groups of conscious rats were pretreated i.c.v. with equimolar doses (3.0-24.4 nmol) of specific receptor antagonists (naloxone HCl, phentolamine HCl, propranolol HCl, yohimbine HCl or prazosin HCl) 10 min before subsequent i.c.v. administration of SS or DMSO/SS or 6.1 nmol of dynorphin A-(1-13). I.c.v. injection of dynorphin A-(1-13) caused a dose-related pressor response, associated temporally with tachycardia. As well, dynorphin evoked feeding activity and some grooming, which occurred when the rats were hypertensive and tachycardic and decreased as heart rate and blood pressure returned to control levels. I.c.v. pretreatment studies indicated that naloxone HCl (12.2 nmol), phentolamine HCl (12.2 nmol) and prazosin HCl (6.1 nmol) blocked the pressor response, tachycardia as well as feeding activity of rats subsequently given dynorphin. The results suggest the pressor and tachycardic effects of conscious rats following i.c.v. dynorphin administration may, in part, be due to behavioral activation (feeding). As well, these data indicate that both opioid as well as alpha 1-adrenergic receptors within the CNS are involved in mediating the pressor, tachycardic and feeding responses of conscious rats given i.c.v. injections of dynorphin A.     

Central nervous system actions of corticotropin-releasing factor on cardiovascular function in the absence of locomotor activity

Studies were performed in conscious and anesthetized Sprague-Dawley rats to examine whether the cardiovascular responses to intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) required concomitant locomotor activation. I.c.v. administration of CRF to conscious animals elicited significant increases in arterial pressure, heart rate, mesenteric resistance, and iliac blood flow, as well as intermittent locomotor, grooming and chewing activity. Intravenous infusion of the anesthetic agent, Saffan, at the minimal dose required to abolish locomotor activity caused slight but significant elevations of heart rate and mesenteric vascular resistance. I.c.v. administration of CRF to anesthetized animals produced delayed, yet significant and sustained increases in the heart rate and arterial pressure, without altering regional blood flow. These results demonstrate that locomotor activation is not requisite for the expression of CRF-induced pressor and tachycardic responses. It is concluded that CRF acts within the central nervous system to influence cardiovascular function in the absence of locomotor activity.     

Pressor effects of systemic administration of methionine and leucine enkephalin in the conscious rat

Experiments were designed using conscious Sprague-Dawley rats to determine the blood pressure (BP) and heart rate (HR) responses to intravenous doses of (1) the adrenal catecholamines noradrenaline (NA) and adrenaline (A), (2) adrenal pentapeptides methionine enkephalin (ME) and leucine enkephalin (LE), (3) combination (i.v.) injections of both ME or LE with NA or A that modulate the hemodynamic responses when the adrenal catecholamines were given alone, and (4) the possible receptor mechanisms mediating the resultant BP and HR response to i.v. pentapeptide administration. NA (0.48 and 2.4 nmol) and A (0.3 and 1.5 nmol) given i.v. evoked potent, dose-related pressor responses associated with reflex bradycardia. ME and LE (1.6 - 48 nmol) elicited transient (10-20 s) increases in mean arterial pressure (MAP), which was associated either with no change in mean heart rate (MHR), such as ME, or with slight bradycardia (i.e., LE). Combining ME or LE (16 nmol) with NA (2.4 nmol) or A (0.3 or 1.5 nmol) did not change MAP and MHR from when these respective doses of NA or A were given alone. However, 16 nmol of ME or LE with a low dose of NA (0.48 nmol) increased the pressor response compared with NA (0.48 nmol) given alone. Other experiments whereby specific receptor blockers (naloxone, diprenorphine, atropine, propranolol, phentolamine or guanethidine) were given i.v. 5 min before subsequent i.v. administration of LE or ME (16 nmol) indicated that only phentolamine or guanethidine could completely suppress the pressor responses of LE and ME. Naloxone and diprenorphine pretreatment attenuated the pressor response of LE but did not affect the BP response to ME.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intravenous morphine infusion (IMF) to drug-naive, conscious rats evokes bradycardic, hypotensive effects, but pressor actions are elicited after IMF to rats previously given morphine

Hemodynamic (blood pressure and heart rate) responses of conscious drug-naive rats were studied following intravenous (i.v.) infusion of sterile saline, morphine sulphate, and then naloxone hydrochloride, as well as of other groups previously injected with morphine sulphate. Those groups chronically given morphine sulphate received twice daily injections of morphine sulphate (5 mg/kg, s.c. per injection) for 3 or 6 days before testing with the i.v. infusion of morphine sulphate. Drugs were infused (135 microL/min) through an indwelling femoral venous catheter via a Harvard infusion pump, and blood pressure was recorded from the abdominal aorta via a femoral arterial catheter. Other pretreatment studies were done to determine the receptor mechanisms mediating the blood pressure responses of drug-naive and chronic morphine-treated rats, whereby equimolar doses (0.32 mumol) of specific receptor antagonists were given as a bolus i.v. injection 5 min after saline but before subsequent infusion with morphine sulphate. Intravenous infusion of morphine sulphate (7.5 mg/kg total over 15 min) to drug-native rats caused a transient but precipitous fall in mean arterial pressure and mean heart rate with an associated rise in mean pulse pressure; these effects were blocked in other groups pretreated with atropine. Interestingly, however, rats chronically injected with morphine sulphate for 3 days previously evoked a transient pressor response when subsequently infused i.v. with morphine sulphate, actions that were blocked in other groups when pretreated i.v. with 0.32 mumol of phentolamine, yohimbine, prazosin, or guanethidine. A greater and persistent pressor response occurred following morphine infusion to groups of rats previously injected over 6 days with morphine sulphate, which was associated with tachycardia during the later stages of the 15-min morphine sulphate infusion period. The prolonged pressor and tachycardic responses of this 6-day chronically injected group were completely blocked in another group pretreated i.v. with both phentolamine and propranolol (0.32 mumol). The results suggest that morphine sulphate infusion to conscious, drug-naive rats evokes classical hypotensive effects due to decreases in mean heart rate caused by activation of parasympathetic vagal activity. With 3 or 6 days of chronic morphine sulphate administration beforehand, subsequent i.v. infusion of morphine sulphate evoked pressor actions felt to be caused by a progressive activation of the sympathetic nervous system.(ABSTRACT TRUNCATED AT 400 WORDS)     

CRF-induced excessive grooming behavior in rats and mice

We studied the grooming response to lateral ventricle injection of CRF in both rats and mice under similar conditions. One microgram of CRF ICV induced a pronounced increase (3- to 4-fold) in the frequency of self-grooming in rats, but only a much smaller (less than 20%) increase in mice. The minimum effective dose of CRF in rats was 300 ng. Although ACTH1-24 induced less grooming in mice than in rats, the difference in potency did not appear to be sufficient to explain the differences between the effectiveness of CRF in the two species. Whereas ACTH increased all types of grooming scored. CRF increased all forms of grooming except flank scratching with the hind limb. The major effect of CRF was to increase the number of episodes of grooming, whereas ACTH1-24 tended to prolong the length of individual episodes. The excessive grooming induced by ICV CRF was not affected by prior treatment with dexamethasone, suggesting that the increased grooming was not due to secondary release of ACTH from the pituitary. Nevertheless, ICV CRF might induce grooming by releasing MSH/ACTH from cerebral storage sites. CRF-induced grooming, like ACTH-induced grooming, was inhibited by naloxone pretreatment. Despite the small qualitative differences, CRF-induced grooming could be due to secondary release of ACTH.     

TRH: Cardiovascular and sympathetic modulation in brain nuclei of the rat

The cardiovascular and sympathetic effects of TRH in discrete cardiovascular-related brain nuclei were studied. Microinjections of TRH were made into the nucleus preopticus medialis (POM) of conscious rats and the nucleus tractus solitarius (NTS) of pentobarbitone-anesthetized, artificially respired rats. POM injections (1 μl, 0.8–80 nM) elicited dose dependent pressor and tachycardic responses which were accompanied by increased levels of norepinephrine (NE) and epinephrine (EPI) in the plasma. These pressor/tachycardic effects of TRH were also elicited in adrenal demedullated (ADM-x) rats, but completely abolished in ADM-x rats pretreated with bretylium (30 mg/kg, IA). NTS injections (0.1 μl, 30 and 150 nM) had a short depressor effect on blood pressure (BP) and a delayed increase in heart rate (HR). From these findings we suggest that the POM, a central nucleus in the AV3V region, may be an important forebrain site for autonomic regulation by TRH, mediated through the sympathetic nervous system.     

Central cardiovascular effects of mammalian neurohypophyseal peptides in conscious rats

To confirm and extend the results of previous studies which demonstrated central cardiovascular effects of vasopressin in anesthetized rats, we determined blood pressure and heart rate changes for 30 minutes after intracerebroventricular injections of arginine vasopressin, arginine vasotocin and oxytocin in conscious rats. As compared to sham injections, significantly greater increases in either systolic or diastolic blood pressure were noted over the 30 minutes which followed the injection of 0.15, 1.0 or 10.0 nM of either vasopressin or vasotocin. In animals given vasopressin, plasma levels of the peptide were determined. There was a substantial increase in plasma vasopressin only after the highest dose. Overall blood pressure responses to doses of oxytocin as high as 100 nM were not significantly different than sham injections. Heart rate following both vasopressin and vasotocin was increased at 0.15 nM, was initially decreased then increased at 1.0 nM and was substantially decreased after the 10.0 nM dose. There was a significant increase in heart rate at the 10.0 nM and 100 nM doses of oxytocin. Dose response curves for systolic blood pressure and heart rate 20 minutes after injection were similar for vasopressin and vasotocin. We conclude that arginine vasopressin has significant central pressor and tachycardic effects in conscious rats, and it is related, at least in part, to the tail structure of the peptide, which is shared with arginine vasotocin.     

Cardiovascular responses to substance P in the nucleus tractus solitarii: microinjection study in conscious rats

The cardiovascular effects of substance P (SP) microinjections in the nucleus tractus solitarii (NTS) were evaluated in conscious rats. We chose this model because it is an effective way to access some of the cardiovascular effects of neurotransmitters in the NTS without the inconvenience of blunting pathways with anesthetic agents or removing forebrain projections by decerebration. The cardiovascular responses to SP injections were also evaluated after chronic nodose ganglionectomy. We found that, in conscious rats, SP microinjections into the NTS induced hypertension and tachycardia. Unilateral and bilateral SP injections into the NTS caused a slow increase in blood pressure and heart rate that peaked 1.5-5 min after injection and lasted for 20-30 min. Nodose ganglionectomy increased the duration of the pressor and tachycardic effects of SP and enhanced the pressor response. These data show that SP in the NTS is involved in pressor pathways. The supersensitivity to SP seen after nodose ganglionectomy suggests that vagal afferent projections are involved in those pressor pathways activated by SP in the NTS.     

Chemical stimulation of the dorsomedial hypothalamus elevates plasma ACTH in conscious rats

The hallmark neuroendocrine response to stress is increased plasma ACTH. Inhibition of neurons in the region of the dorsomedial hypothalamus (DMH) attenuates experimental air stress-induced elevation of heart rate (HR), mean arterial pressure (MAP), and plasma ACTH. We hypothesized that, under basal conditions, stimulation of the DMH would mimic the neuroendocrine and cardiovascular response to air stress. We examined the effects of unilateral microinjection (100-nl vol) of bicuculline methiodide (BMI, 10 pmol), kainate (KA, 1 or 3 pmol), and N-methyl-D-aspartate (5 pmol) into the DMH or the paraventicular nucleus (PVN) on HR, MAP, locomotor activity, and plasma ACTH in conscious rats. Chemical stimulation of the DMH with KA or BMI produced increased locomotor activity and effects on HR, MAP, and plasma ACTH that together mimicked the pattern seen in experimental stress. Similar treatment in the PVN produced only small increases in MAP. Thus activation of neurons in the region of the DMH results in increased secretion of ACTH along with other changes typically seen in experimental stress.     

Respiratory effects of pressor and depressor agents in conscious rats

We hypothesized that the respiratory baroreflex in conscious rats is either more transient, or has a higher pressure threshold than in other species. To characterize the effect of arterial pressure changes on respiration in conscious rats, ventilation (V) was measured by the plethysmographic technique during injections, or infusions, of pressor and depressor agents. Bolus injections of angiotensin II (Ang II) or arginine vasopressin (AVP), transiently increased mean arterial pressure (MAP; mean +/- SE) 43+/-6 and 28+/-5 mm Hg (1 mm Hg = 133.3 Pa), respectively, and immediately reduced tidal volume (Vt) and, in the case of AVP, V. In contrast, by 10 min of a sustained elevation of MAP (40+/-3 mm Hg) with infusion of Ang II, Vt, f, and V were not different from control levels. Bolus injection of sodium nitroprusside (SNP) to lower MAP (-28+/-3 mm Hg) immediately increased breathing frequency (f) and V, whereas sustained infusion of SNP to lower MAP (-21+/-3 mm Hg) did not change for V at 10 and 20 min. In conscious rats, both injection and infusion of the pressor agent PE (+40 to 50 mm Hg) stimulated f and V; this contrasted with anesthetized rats where PE inhibited f and V, as reported by others. In conscious rats, respiratory responses associated with baroreflexes adapt rapidly and, in the case of PE, can be overridden by some other mechanism.     

Thermoregulatory (core, surface and metabolic) responses of unrestrained rats to repeated POAH injections of beta-endorphin or adrenocorticotropin

Repeated preoptic-anterior hypothalamic (POAH) injections of saline and 10 or 25 micrograms/microliters of beta-endorphin or ACTH were given to groups of male Sprague-Dawley rats. One hr after the fifth injection of beta-endorphin or ACTH, each rat received a POAH injection of naloxone HCl (10 micrograms/microliters). Core (Tre-rectal) and surface (Tt-tail) temperatures, metabolic (VO2) and behavioral responses were recorded 30 min before and 60 min after each drug injection. The initial POAH injection of either dose of beta-endorphin produced a hyperthermia. Peak hyperthermia was reduced in the group given 10 micrograms/microliters of beta-endorphin repeatedly. TtS rose after each beta-endorphin injection but temporally lagged Tre increases. Metabolic rate (VO2) was increased with repeated POAH injections of beta-endorphin. Naloxone reduced the elevated Tre seen with beta-endorphin by increasing Tt's further and reducing VO2. POAH administration of ACTH evoked only a slight hyperthermic Tre response, but elevated TtS and VO2S, due to enhanced grooming and explorative behavior. With repeated ACTH injections, TreS did not change from those on the first day as TtS and VO2 remained enhanced. Naloxone reduced VO2 and TtS of the ACTH-treated rats but TreS still were unchanged. Results suggest that the hyperthermia of unrestrained rats given an acute as opposed to repeated POAH beta-endorphin injections is mediated by different effector mechanisms. With the doses used, the slight and unchanging TreS seen with ACTH occurred because this peptide increased heat production due to locomotor activation yet also exaggerated heat loss by vasodilating the peripheral vasculature.     

Effect of central naloxone on hormone and blood pressure responses to hemorrhage in conscious sheep

The role of the brain opioid system in the control of hypothalamic-pituitary-adrenal activity was studied in 10 conscious sheep with an indwelling cannula in a cerebral lateral ventricle. On separate days, sheep received infusions of artificial CSF (control) and the opiate antagonist, naloxone (100 micrograms/hr) before and during acute moderate hemorrhage (15 ml/kg over 10 min). Infusion of naloxone before hemorrhage raised plasma ACTH and resulted in a significant increase in cortisol compared to the control infusion. In contrast, ACTH and cortisol responses to hemorrhage tended to be blunted by central naloxone infusion. The responses of vasopressin, aldosterone and the catecholamines remained unaffected by naloxone. The fall in blood pressure and the rise in heart rate accompanying hemorrhage were likewise unaltered. These results suggest that brain opioid peptides have an inhibitory effect on basal ACTH secretion but do not play a major role in modulating the hemodynamic or pituitary-adrenal responses to acute moderate hemorrhage in conscious sheep.     

Inhibition of brain nitric oxide synthesis enhances and prolongs the hypertensive effect of centrally administered interleukin-1beta in rats

The present study was designed to find out whether brain nitric oxide (NO) influences hemodynamic response to intracerebroventricular (ICV) infusion of interleukin-1 beta (IL-1beta). Mean arterial blood pressure (MAP) and heart rate (HR) were recorded in seven series of experiments performed on conscious Sprague-Dawley rats receiving during 60 min ICV infusion of: 0.9% NaCl (5 microl/h; series 1), IL-1beta (100 ng/h; series 2), NO synthase inhibitor (L-NAME, 1mg/h; series 3), IL-1beta together with L-NAME (series 4), IL-1beta together with inactive isomer of NO synthase inhibitor (D-NAME, 1mg/h; series 5), NO donor (SNAP, 40 microg/h; series 6) and IL-1beta together with SNAP (series 7). ICV infusion of saline did not influence MAP while administration of IL-1beta as well as IL-1beta together with D-NAME elicited a significant, though transient, increase in MAP. In series 4, combined infusion of IL-1beta and L-NAME exerted an increase in MAP, which persisted until the end of the experiment and was significantly higher than in series 2 and 5. In series 7, infusion of SNAP together with IL-1beta abolished the pressor effect of IL-1beta. HR was not significantly altered in any of the experimental series. These results demonstrate that inhibition of NO synthesis in the brain enhances and prolongs the pressor response to IL-1beta, whereas concomitant administration of NO donor abolishes the hemodynamic effect of IL-1beta. Therefore, we conclude that NO generated in the brain is involved in buffering the pressor response to IL-1beta.     

Hemodynamic responses of conscious rats following intrathecal injections of prodynorphin-derived opioids: independence of action of intrathecal arginine vasopressin

Experiments were conducted (i) to determine the hemodynamic (blood pressure and heart rate) responses of conscious rats following intrathecal (IT) administration of endogenous prodynorphin-derived opioids into the lower thoracic space, (ii) to identify the receptors involved in mediating their cardiovascular responses, and (iii) to reveal any possible hemodynamic interactions with the neuropeptide arginine vasopressin. Male Sprague-Dawley rats were surgically prepared with femoral arterial and venous catheters as well as a spinal catheter (into lower thoracic region, T9-T12). After recovery, hemodynamic responses were observed in conscious rats for 5-10 min after IT injections of artificial cerebrospinal fluid (CSF) solution, prodynorphin-derived opioids (dynorphin A, dynorphin B, dynorphin A (1-13), dynorphin A (1-10), alpha- and beta-neoendorphin, leucine enkephalin (LE), methionine enkephalin (ME), arginine vasopressin (AVP), or norepinephrine (NE)). IT injections of AVP (10 or 20 pmol), dynorphin A (1-13), or dynorphin A (10-20 nmol) caused pressor effects associated with a prolonged and significant bradycardia. Equimolar (20 nmol) concentrations of LE, ME, alpha- and beta-neoendorphin, and dynorphin A (1-10) caused no significant blood pressure or heart rate changes. Combined IT injections of dynorphin A (1-13) and AVP caused apparent additive pressor effects when compared with the same dose of either peptide given alone. IT infusion of the specific AVP-V1 antagonist d(CH2)5Tyr(Me)AVP before subsequent IT AVP, dynorphin A (1-13), or NE administration inhibited only the subsequent pressor responses to AVP. The kappa-opioid antagonist (Mr2266) infused IT blocked the pressor actions of subsequent dynorphin A administration and not AVP or NE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiovascular mechanisms activated by microinjection of baclofen into NTS of conscious rats

The peripheral mechanisms responsible for pressor response produced by microinjections of baclofen (GABA(B) agonist) into the nucleus tractus solitarii (NTS) of conscious rats were studied. Bilateral microinjections of baclofen (10-1,000 pmol/100 nl) produced a dose-related increase in mean arterial pressure (MAP) and heart rate. The maximal response was observed after 15 min. Intravenous injection of prazosin decreased MAP to control levels. Subsequent treatment with Manning compound (vasopressin receptor antagonist; iv) produced an additional decrease in MAP. In a different group of rats, vasopressin antagonist was injected first and MAP was significantly decreased; however, it remained elevated compared with prebaclofen injection levels. Subsequent treatment with prazosin abolished the baclofen-induced pressor response. Reductions in baclofen-induced pressor response with prazosin treatment were followed by a reflex tachycardia in animals that received a 100 pmol/100 nl dose of baclofen. The tachycardia was not observed with a dose of 1,000 pmol/100 nl. The pressor response induced by microinjection of baclofen into the NTS of conscious rats may be produced by both increases in sympathetic tonus and vasopressin release.     

Comparison of TRH and its analog (NS-3) in thermoregulatory and cardiovascular effects.

The effects of TRH and its metabolically stable analog NS-3 [(3R,6R)-6-methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl-L-pro linamide tetrahydrate] on thermoregulation and circulatory control have been investigated. Both NS-3 (1-100 ng/kg ICV) and TRH (0.1-10 micrograms/kg ICV) increased rectal temperature and metabolic rate with a transient cutaneous vasoconstriction in conscious rabbits. They also increased arterial blood pressure, heart rate, respiratory rate, and renal sympathetic nerve activity (RSNA) in urethane-anesthetized rabbits. Ten ng/kg of NS-3 and 10 micrograms/kg of TRH had comparable hyperthermic, pressor, and tachycardic activities, while the relative potency of NS-3 to increase RSNA was greater and that to increase metabolic rate was smaller than the other effects. In conclusion, NS-3 was more potent than TRH in all of the effects measured, but there was a dissociation in the relative potency of NS-3 in the different autonomic effects.     

Cold pressor test in the rat: medullary and spinal pathways and neurotransmitters

This study was designed to delineate the medullary and spinal pathways mediating the cardiovascular responses to cold pressor test (CPT) and to identify neurotransmitters in these pathways. Experiments were done in barodenervated, urethane-anesthetized, male Wistar rats. The CPT was performed by immersing the limbs and ventral half of the body of the rat in ice-cold water (0.5 degrees C) for 2 min. CPT elicited an immediate increase in mean arterial pressure (MAP), heart rate (HR), and greater splanchnic nerve activity (GSNA). Bilateral blockade of ionotropic glutamate receptors (iGLURs) in the rostral ventrolateral medullary pressor area (RVLM) significantly attenuated the CPT-induced responses. Bilateral blockade of gamma-aminobutyric acid (GABA) receptors, but not iGLURs, in the nucleus ambiguus (nAmb) significantly reduced the CPT-induced increases in HR, but not MAP. Blockade of spinal iGLURs caused a significant reduction in CPT-induced increases in MAP and GSNA, whereas the increases in HR were reduced to a lesser extent. Combination of the blockade of spinal iGLURs and bilateral vagotomy or intravenous atropine almost completely blocked CPT-induced tachycardia. Midcollicular decerebration significantly reduced CPT-induced increases in MAP and HR. These results indicated that: 1) CPT-induced increases in MAP, HR, and GSNA were mediated by activation of iGLURs in the RVLM and spinal cord, 2) activation of GABA receptors in the nAmb also contributed to the CPT-induced tachycardic responses, and 3) brain areas rostral to the brain stem also participated in the CPT-induced pressor and tachycardic responses.     

Role of spinal V1a receptors in regulation of arterial pressure during acute and chronic osmotic stress

Vasopressinergic neurons in the paraventricular nucleus project to areas in the spinal cord from which sympathetic nerves originate. This pathway is hypothesized to be involved in the regulation of mean arterial pressure (MAP), particularly under various conditions of osmotic stress. Several studies measuring sympathetic nerve activity support this hypothesis. However, the evidence that spinal vasopressin influences MAP under physiological or pathophysiological conditions in conscious animals is limited. The purpose of this study was to investigate, in conscious rats, if the increases in MAP during acute or chronic osmotic stimuli are due to activation of spinal vasopressin (V1a) receptors. Three conditions of osmotic stress were examined: acute intravenous hypertonic saline, 24- and 48-h water deprivation, and 4 wk of DOCA-salt treatment. Rats were chronically instrumented with an indwelling catheter for intrathecal injections and a radiotelemeter to measure MAP. In normotensive rats, intrathecal vasopressin and V1a agonist increased MAP, heart rate, and motor activity; these responses were blocked by pretreatment with an intrathecal V1a receptor antagonist. However, when the intrathecal V1a antagonist was given during the three conditions of osmotic stress to investigate the role of "endogenous" vasopressin, the antagonist had no effect on MAP, heart rate, or motor activity. Contrary to the hypothesis suggested by previous studies, these findings indicate that spinal V1a receptors are not required for elevations of MAP under conditions of acute or chronic osmotic stress in conscious rats.