心钠素对卒中易感型自发性高血压大鼠血浆和脑组织加压素的影响

为研究心钠素(ANF)和精氨酸加压素(AVP)的相互作用在原发性高血压发病中的意义,对卒中易感型自发性高血压大鼠(SHRsp)和对照大鼠(WKY)侧脑室(icv)或静脉(iv)注射人ANF-(99-126)观察其对血浆、下丘脑和垂体AVP含量以及平均动脉压(MAP)和尿量(UV)、尿钠(U_(Na)V)排泌的影响。静脉注射ANF后10min,SHRsp和WKY大鼠的MAP分别下降9.4％和12.2％(P<0.05),UV分别增加9和20倍(P<0.01),U_(Na)V增加16和29倍(P<0.01)。侧脑室注射ANF对两种大鼠的MAP、UV和U_(Na)V排泌均无明显作用。静脉或侧脑室注射ANF均使两种大鼠的血浆AVP水平明显下降,其中SHRsp的血浆AVP浓度下降程度(iv,-58％;icv,-31％)弱于WKY大鼠(iv,-80％;icv,-65％),下丘脑AVP含量在两种大鼠中都明显增加,而垂体AVP含量无明显变化。 结果表明,人ANF-(99-126)有明显的抑制AVP释放和降压、利尿、利纳作用,而SHRsp对这些作用的敏感性都降低,提示SHRsp对ABF的反应减弱可能在自发性高血压大鼠的发病中具有一定的意义。     

Effect of atrial natriuretic factor on plasma vasopressin in conscious rats

An intravenous (IV) bolus injection (10 μg) of synthetic rat atrial natriuretic factor [ANF (Arg 101-Tyr 126)] into normal conscious Sprague-Dawley rats produced a significant decrease of plasma arginine vasopressin (AVP) while 1-, 2-, and 5-μg doses exerted no such effect. Mean arterial blood pressure (MAP) was lowered about 15 mmHg by an IV 10 μg bolus injection of ANF. When plasma AVP rose significantly in rats exposed to such osmotic stimuli as 600 mM NaCl and 900 mM mannitol intraperitoneally (IP), subsequent IV injection of ANF (10 μg) markedly depressed this parameter. Lower doses of ANF were ineffective against 600 mM NaCl IP. The significant elevation of plasma AVP levels by hypertonic sucrose 900 mM IP was not modified by ANF (10 μg). Blood pressure remained unchanged after IP administration of various osmotic stimuli, except mannitol, and in all these experiments an IV bolus of ANF exerted a lowering effect on MAP. Seventy-two hr water deprivation (mixed osmotic and volume stimulus) resulted in elevated plasma AVP levels which were unaffected by an IV bolus injection of ANF at doses of 0.06–10 μg. Immunoreactive ANF (IR-ANF) rose in plasma to 39.3±13 ng/ml 1 min after an IV bolus injection of 10 μg ANF, dropping to 1.01±0.2 ng/ml after 5 min and to 0.32±0.01 ng/ml after 10 min (when ANF and AVP interactions were studied), but still remained approximately six times higher than in control rats. These results suggest that, in the conscious rat, only pharmacological levels of ANF observed after an IV bolus infusion may influence both resting and osmotically-stimulated AVP levels.     

精氨酸加压素对大鼠抗体产生和淋巴细胞增殖的上调作用

大鼠侧脑室注射１００ｎｇ精氨酸加压素（ＡＶＰ）,用ＥＬＩＳＡ法检测血中对鸡卵白 白抗原产生的ＩｇＧ抗体水平。结果显示,ＩｇＧ水平高于对照,而ＡＶＰ的Ｖ１受体阻断剂ＤＰＡＶＰ则可阻断此作用;ｉｃｖ８００ｎｇＡＶＰ,大鼠的ＳＲＢＣ溶血素 水平高于对照;ｉｃｖ１００ｎｇ、８００ｎｇＡＶＰ２ｈ后,脾淋巴细胞对ＭＴＴ产生的颜色反应均比对照增加,而ＤＰＡＶＰ可阻断之;ｉｃｖ８００ＡＶＰ２ｈ后,脾淋巴细胞对ＭＴ     

Aminopropionic acid receptors in paraventricular nucleus mediate pressor and vasopressin responses to endothelin-1 in subfornical organ

Endothelin-1 (ET-1) acts at selected brain loci to elicit a pressor response and secretion of vasopressin (AVP). Glutamatergic receptors of the N-methyl-D-aspartate (NMDA) subtype mediate ET-1-induced AVP secretion in vitro, but the role of glutamatergic receptors in the pressor response and the secretion of AVP in vivo has not been studied. We hypothesized that both the pressor response and AVP secretion in response to ET-1 microinjection into subfornical organ (SFO) would be suppressed by ionotropic glutamatergic receptor antagonists in the paraventricular nucleus (PVN). Sinoaortic denervated male Long Evans rats were equipped with intracerebral cannulae directed into the SFO and the magnocellular region of the PVN bilaterally. Experiments were performed 5 days later in conscious rats. Direct injection of 5 pmol ET-1 into the SFO resulted in a 20 +/- 3 mm Hg increase in mean arterial pressure (MAP) (+/- SE) and a 14.1 +/- 0.3 pg/ml increase in the mean plasma AVP level (+/- SE) (P < 0.001 vs. artificial CSF) that was blocked by selective ET(A) inhibition. Neither the pressor response nor the increase in plasma AVP in response to ET-1 was altered despite prior injection of the NMDA blocker diclozipine (5 microg, MK801) into PVN bilaterally. In contrast, bilateral PVN injection with 6-cyano-7-nitroquinoxaline-2,3-dione (40 nmol, CNQX) prevented the pressor response (MAP +/- SE, - 4 +/- 4 mm Hg) and also inhibited AVP secretion (mean AVP level +/- SE, 0.16 +/- 0.50 pg/ml) (P < 0.001 vs. vehicle in PVN after injection of ET-1 into SFO). These findings support the conclusion that both the pressor response and AVP secretion in response to ET-1 acting at the SFO are mediated by a non-NMDA, most likely an aminopropionic acid glutamatergic receptor within the PVN.     

Facilitation of Feedback Inhibition Through Blockade of Glucocorticoid Receptors in the Hippocampus

In the present study the effects of intracerebroventricular (icv) and intrahippocampal administration of corticosteroid antagonists on basal hypothalamic-pituitary-adrenal (HPA) activity around the diurnal peak were compared in male Wistar rats. In two separate experiments the glucocorticoid receptor (GR) antagonist RU 38486 and the mineralocorticoid receptor (MR) antagonist RU 28318 were tested. One hour after GR antagonist injection, significant increases in plasma ACTH and corticosterone levels were observed in the icv treated rats, when compared to vehicle. In contrast, a significant decrease in ACTH levels, and a slight, but non-significant decrease in corticosterone concentrations were attained one hour after intrahippocampal injection of the GR antagonist. Injection of the MR antagonist, on the other hand, resulted in enhanced ACTH and corticosterone levels irrespective of the site of injection. These findings suggest that negative feedback inhibition at the circadian peak involves hippocampal MRs and extrahippocampal (hypothalamic) GRs. The latter feedback inhibition overrides a positive feedback influence exerted by endogenous corticosteroids through hippocampal GRs.     

Adrenomedullin 2 (AM2)/intermedin is a more potent activator of hypothalamic oxytocin-secreting neurons than AM possibly through an unidentified receptor in rats

Central administration of either adrenomedullin 2 (AM2) or adrenomedullin (AM) activates hypothalamic oxytocin (OXT)-secreting neurons in rats. We compared AM2 with AM, given intracerebroventricularly (icv), across multiple measures: (1) plasma OXT levels in conscious rats; (2) blood pressure, heart rate and circulating catecholamine levels in urethane-anesthetized rats; and (3) the expression of the c-fos gene in the supraoptic (SON) and the paraventricular nuclei (PVN). We also tested the effects of the AM receptor antagonist, AM(22-52) and calcitonin gene-related peptide (CGRP) antagonist, CGRP(8-37) on these measures. Plasma OXT levels at 10 min after icv injection of AM (1 nmol/rat) were increased (compared with vehicle), but OXT levels after AM2 (1 nmol/rat) were nearly double the levels seen after AM injection. OXT levels remained elevated at 30 min. Pretreatment with AM(22-52) (27 nmol/rat) and CGRP(8-37) (3 nmol/rat), nearly abolished the increase in plasma OXT level after AM injection, but partially blocked OXT level changes due to AM2. Increases in blood pressure, heart rate and circulating catecholamines were all greater in response to central AM2 than to AM at the same dose. In situ hybridization histochemistry showed that both AM2 and AM induced expression of the c-fos gene in the SON and the PVN, but AM(22-52)+CGRP(8-37) could only nearly abolish the effects of centrally administered AM. These results suggest that the more potent central effects of AM2 and only partial blockade by AM/CGRP receptor antagonists may result from its action on an additional, as yet unidentified, specific receptor in the central nervous system.     

Centrally administered adrenomedullin 2 activates hypothalamic oxytocin-secreting neurons, causing elevated plasma oxytocin level in rats

We examined the effects of intracerebroventricular (i.c.v.) administration of adrenomedullin 2 (AM2) on plasma oxytocin (OXT) and arginine vasopressin (AVP) levels in conscious rats. Plasma OXT levels were markedly increased 5 min after i.c.v. administration of AM2 (1 nmol/rat) compared with vehicle and remained elevated in samples taken at 10, 15, 30, and 60 min. By contrast, plasma AVP levels were not significantly elevated in samples taken between 5 and 180 min after i.c.v. administration of AM2 except at the 30-min time point. Fos-like immunoreactivity (Fos-LI) was observed in various brain areas, including the paraventricular (PVN) and the supraoptic nuclei (SON) after i.c.v. administration of AM2 (2 nmol/rat) in conscious rats (measured at 90 min post-AM2 infusion). Dual immunostaining for OXT/Fos and AVP/Fos showed that OXT-LI neurons predominantly exhibited nuclear Fos-LI compared with AVP-LI neurons in the PVN and the SON. In situ hybridization histochemistry showed that i.c.v. administration of AM2 (0.2, 1, and 2 nmol/rat) caused marked induction of the expression of the c-fos gene in the PVN and the SON. This induction was significantly reduced by pretreatment with both the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) (3 nmol/rat) and the AM receptor antagonist AM-(22-52) (27 nmol/rat). These results suggest that centrally administered AM2 mainly activates OXT-secreting neurons in the PVN and the SON, at least in part through the CGRP and/or AM receptors with marked elevation of plasma OXT levels in conscious rats.     

Corticotropin-releasing factor receptor antagonist: effects on the autonomic nervous system and cardiovascular function

The corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical [Glu27]-corticotropin-releasing factor 9-41 (CRF 9-41) has been assessed for its ability to modify plasma concentrations of epinephrine and norepinephrine, mean arterial pressure (MAP) and heart rate (HR). Basal concentrations of epinephrine and norepinephrine were not altered by lateral ventricular (icv) administration of CRF 9-41. However, this CRF antagonist, given icv, attenuated the rise of plasma epinephrine following 30% hemorrhage and insulin-induced hypoglycemia. CRF 9-41 did not alter the increased plasma concentrations of epinephrine or norepinephrine following icv administration of bombesin. Icv administration of CRF 9-41 blunted CRF-induced elevation of MAP and HR in normal animals. However, this CRF antagonist did not modify the MAP or HR in spontaneously hypertensive rats. Similarly, this CRF antagonist administered to Sprague-Dawley rats neither prevented the rise of MAP or HR following electrical stimulation of the central nucleus of the amygdala, nor did it affect nitroprusside-induced hypotension and tachycardia.     

Pressor responses in rats following intravenous dynorphin A(1-13) administration are blocked by AVP-V1 receptor antagonism

Hemodynamic (blood pressure and heart rate) experiments were conducted in conscious and/or anesthetized male Sprague-Dawley (S.D.), heterozygous and homozygous Brattleboro rats given intravenous (iv) dynorphin A(1-13), arginine vasopressin (AVP), norepinephrine (HCl, (NE) or sterile saline before and 10 min after an iv bolus injection of a specific receptor antagonist. These receptor blockers (kappa receptor antagonist Mr2266, alpha adrenoceptor antagonist phentolamine HCl or the AVP-V1 receptor antagonist d(CH2)5Tyr-(Me)AVP were given in equimolar concentrations (15 nmol/kg iv). In all conscious S.D. groups, iv injection of AVP (60 pmol/kg), NE (12.5 nmol/kg) and dynorphin A(1-13) (60 nmol/kg) evoked significant increases in mean arterial pressure (MAP) associated with concomitant bradycardia. The hemodynamic responses to 'both' AVP and dynorphin A(1-13) were blocked if given subsequent to AVP-V1 administration but not following phentolamine or Mr2266 pretreatment. The pressor and bradycardic responses of conscious heterozygous and homozygous Brattleboro rats after iv AVP or dynorphin again were only blocked by the AVP-V1 receptor antagonist. Anesthetized heterozygous and homozygous Brattleboro rats again showed pressor responses following iv AVP, NE or dynorphin A(1-13) but with slight or no associated bradycardia. The rise in blood pressure with AVP 'and' dynorphin A(1-13) in these groups also was only blocked by the d(CH2)5Tyr(Me)AVP antagonist. The results indicate that the pressor responses of rats given intravenous dynorphin A(1-13) involve the interaction of AVP-V1 receptors and suggest a functional interaction of these two neuropeptides in the modulation of vascular tone.     

Central G-alpha subunit protein-mediated control of cardiovascular function, urine output, and vasopressin secretion in conscious Sprague-Dawley rats

The role(s) of central Galpha-proteins in the regulation of cardiovascular and renal function is unknown. We examined how inhibition/downregulation of central Galphai/Galphao, Galphaz or Galphaq proteins altered the characteristic cardiovascular (depressor), renal excretory (diuretic), and plasma AVP (inhibitory) responses to intracerebroventricular injection of nociceptin/orphanin FQ (N/OFQ) in rats. Before investigation, rats were pretreated intracerebroventricularly with saline vehicle (5 microl, 48 h, n=6), pertussis toxin (PTX; 48-h, 1 microg, n=6), or Galphaz, Galphaq, or scrambled oligodeoxynucleotide (ODN) (25 microg, 24 h, n=6 per group). On the study day, intracerebroventricular N/OFQ (5.5 nmol) or vehicle (5 microl) was injected into pretreated conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were recorded, and urine was collected for 90 min. In vehicle or scrambled ODN groups, intracerebroventricular N/OFQ decreased MAP and HR and produced water diuresis (sensitive to UFP-101, N/OFQ receptor antagonist). The hypotension and bradycardia, but not diuresis, to N/OFQ were abolished in PTX-pretreated rats. In contrast, intracerebroventricular ODN pretreatment markedly blunted (Galphaz) or augmented (Galphaq) the diuresis to intracerebroventricular N/OFQ. In separate studies, the action of central N/OFQ to decrease plasma AVP levels in na?ve water-restricted rats was differentially altered by intracerebroventricular Galphaz ODN (blunted) and Galphaq ODN (augmented) pretreatment. These studies demonstrate central Galphai/Galphao activity mediates intracerebroventricular N/OFQ's cardiovascular depressor function. Alternatively, central Galphaz (inhibitory) and Galphaq (stimulatory) activity differentially modulates AVP release to control the pattern of diuresis to intracerebroventricular N/OFQ. These findings highlight the novel selective central Galpha-subunit protein-mediated control of cardiovascular vs. renal excretory function.     

Neuromedin S exerts an antidiuretic action in rats

We recently identified neuromedin S (NMS) as an endogenous ligand for the FM-4/TGR-1 receptor. Here, we examined the possible involvement of central NMS in regulation of urinary output and vasopressin (AVP) release in rats. Intracerebroventricular (icv) injection of NMS induced a dose-dependent increase in the plasma level of AVP, followed by a decrease of nocturnal urinary output. Expression of cFos after icv injection of NMS was observed in the supachiasmatic nucleus (SCN), arcuate nucleus, paraventricular nucleus (PVN), and supraoptic nucleus (SON). The cFos expressing cells in PVN and SON, but not SCN, were then double-stained using antibodies against the vasopressin. On the other hand, icv injection of neuromedin U, which also binds to the FM-4/TGR-1 receptor, required a concentration ten times higher than that of NMS in order to exert the same antidiuretic potency. These results suggest that central NMS may exert a physiological antidiuretic action via vasopressin release.     

The effect of a neuropeptide Y antagonist, BIBP 3226, on short-term arterial pressure control in conscious unrestrained rats with congestive heart failure

The effects of a neuropeptide Y (NPY) Y1-receptor antagonist (BIBP 3226) on mean arterial pressure (MAP) and heart rate were investigated in conscious unrestrained rats with chronic congestive heart failure. The rats were randomly assigned to 2 groups, and received either BIBP 3226 or its inactive enantiomer (BIBP 3435) as an intravenous infusion (6 mg/kg/h for 1.5 h, respectively). Before, during and after the infusion, rats were stressed with a jet of air and received a bolus injection of NPY (2 nmol/kg iv.). There was no difference between the 2 groups in resting MAP and heart rate before, during or after infusion (BIBP 3226 vs. BIBP 3435). The effects of exogenous NPY on MAP were significantly attenuated in BIBP 3226 group during and 1 h after the infusion (p<0.05). The tissue NPY levels in heart, adrenal gland and kidney in heart failure rats were not different from those in sham-operated rats. The results suggest that Y1-receptor mechanisms are of minor importance in the short-term control of basal MAP and heart rate in conscious unrestrained rats with congestive heart failure.     

Pressor doses of vasopressin result in only transient elevations in plasma peptide levels

We recently reported that neuronostatin, a novel neuropeptide, biphasically increased mean arterial pressure, first through the activation of the sympathetic nervous system followed by the release of vasopressin. In those experiments, we found that centrally administered neuronostatin increased plasma vasopressin levels only 2-3 times greater than levels observed in saline-treated controls, and that the increase in mean arterial pressure (approximately 15 mm Hg) could be blocked by pretreatment with a V1-vasopressin antagonist. Here we report the relationship between two to three fold elevations in plasma vasopressin levels and concomitant changes in mean arterial pressure in conscious, unrestrained male rats. We injected increasing doses of vasopressin (5, 20, and 100 ng/kg, intra-arterially) and measured both changes in plasma vasopressin levels and the elevation in mean arterial pressure achieved. At 5-min post injection, plasma levels of vasopressin and mean arterial pressures were similar to those observed following central neuronostatin administration in our earlier study. Thus we conclude that small increases in circulating vasopressin levels can result in significant elevations in mean arterial pressure at least in the conscious rat.     

Central cardiovascular effects of baclofen in spontaneously hypertensive rats

This study was conducted to investigate the effects of centrally administered baclofen on blood pressure and heart rate in conscious spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Administration of baclofen (1.0 microgram/kg) into the lateral cerebral ventricle (icv) produced an increase in mean arterial pressure (MAP) in both SHR and WKY rats. The increase in MAP was significantly lower in SHR (13 +/- 3 mmHg) when compared with WKY (27 +/- 5 mmHg). The changes in heart rate (HR) were variable, from no change to a very small increase and did not differ significantly between SHR and WKY rats. The ability of baclofen to interfere with baroreceptor reflexes was also tested in separate experiments. In SHR, icv injection of baclofen (1.0 microgram/kg) significantly suppressed the pressor response and bradycardia evoked by phenylephrine 3.0 micrograms/kg iv, whereas in WKY, the pressor and HR responses to similar injections of phenylephrine were not affected by icv baclofen. Similarly, baclofen treatment modified hypotensive response and reflex tachycardia induced by nitroprusside (10.0 micrograms/kg) iv in SHR but not in WKY rats. Administration of sympathetic ganglionic blocker hexamethonium (HEX; 25 mg/kg) iv produced an equivalent decrease in MAP between SHR and WKY following icv injection of baclofen (1.0 microgram/kg). These results suggest that the effects of baclofen on the baroreceptor reflexes in SHR may not be mediated by a change in peripheral sympathetic tone.     

中枢精氨酸加压素在大鼠促肾上腺皮质激素释放激素释放激素引起发热机制中的作用

实验对大鼠进行第三脑室和脑腹中隔区插管,用数字体温计测量大鼠的结肠温度,用放射免疫分析法测定脑中隔区精氨酸加压素（arginine vasopressin,AVP）含量,观察脑中隔区AVP在大鼠促肾上腺皮质激素释放激素（corticotrophin releasing hormone,CRH）性发热机制中的作用。结果发现：脑室注射CRH（5.0μg）引起大鼠结肠温度明显升高,同时明显增高脑中隔区AVP的含量。脑腹中隔区注射AVP V1受体拮抗剂本身并不导致大鼠结肠温度明显改变,但能显著增强脑室注射CRH引起的发热反应。而且,腹中隔区注射AVP显著抑制大鼠CRH性发热。结果提示：发热时CRH是引起脑腹中隔区AVP释放的因素之一,脑腹中隔区内源性AVP抑制中枢注射CRH引起的体温升高。     

Action sites of adrenomedullin in the rat brain: functional mapping by Fos expression.

The effects of intracerebroventricular (icv) administration of adrenomedullin (AM) and proadrenomedullin NH2-terminal 20 peptide (PAMP) on the expression of Fos in the central nervous system (CNS) were examined in conscious rats, using immunohistochemistry. Fos-like immunoreactivity (LI) was detected in various brain areas of the rats, including the supraoptic nucleus, the paraventricular nucleus, the locus coeruleus, the area postrema and the nucleus of the tractus solitarius 90 min after icv administration of AM. Few cells with Fos-LI were found in the CNS 90 min after icv administration of saline. Fos-LI was also detected in the various hypothalamic areas after icv administration of PAMP. These results suggest that centrally administered AM and PAMP may cause physiological responses through the activation of a neural network in the hypothalamus and the brainstem.     

Cardiovascular responses to exercise in the rat: role of corticotropin-releasing factor

The effects of intracerebroventricular (icv) administration of a corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical CRF, on systemic and regional hemodynamic adjustments to exercise were studied in conscious rats. On consecutive days, rats received saline icv, alpha-helical CRF icv, and no treatment 30 min before treadmill exercise (TMX). Increases in heart rate (HR) and mean arterial pressure (MAP) in response to TMX (16.1-28.6 m/min) were similar after icv administration of saline or no treatment. In rats receiving saline icv or no treatment, estimated vascular resistance increased in the mesenteric and renal regions and declined in the iliac (hindlimb) region. After icv administration of alpha-helical CRF9-41, HR and MAP responses during TMX were significantly attenuated. In addition, TMX-induced elevations of estimated mesenteric vascular resistance and iliac blood flow velocity were blunted after CRF receptor blockade. These altered cardiovascular and hemodynamic responses were ultimately reflected in the animals' compromised ability to run. The results suggest that the central nervous system actions of endogenous CRF are necessary for the full expression of the cardiovascular adjustments to TMX in the conscious rat.     

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.     

Differential cardiovascular effects of central clonidine and B-HT 920 in conscious rats

The effect of intracerebroventricular (i.c.v.) injection of the alpha 2-adrenoceptor agonists clonidine and B-HT 920 on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of noradrenaline and adrenaline was examined in conscious unrestrained rats. The injection of 1.0 microgram clonidine significantly decreased MAP and slightly decreased HR. Plasma noradrenaline and adrenaline levels were slightly but not significantly decreased after the injection of 1 microgram clonidine. In contrast, the injection of 0.1-10.0 micrograms B-HT 920 increased MAP and decreased HR. Plasma noradrenaline and adrenaline levels were slightly increased after the injection of the 1- and 10-micrograms doses. The i.c.v. injection of the alpha 2-antagonist rauwolscine slightly but not significantly increased MAP and plasma noradrenaline and adrenaline levels. The responses to i.c.v. injection of clonidine and B-HT 920 were not changed by prior administration of rauwolscine. Neither the pressor response to B-HT 920 nor the depressor response to clonidine was abolished by rauwolscine, suggesting that neither response was mediated by alpha 2-adrenoceptors.