SELECTIVE DEVELOPMENT OF TOLERANCE TO β-ADRENOCEPTOR AGONISTS IN SKELETAL MUSCLE AS COMPARED WITH AIRWAY SMOOTH MUSCLE FROM THE GUINEA-PIG

1. Guinea-pig were fed with a diet containing terbutaline or placebo for 4--5 days. The trachea, soleus muscle and the extensor digitorum longus (EDL) from these animals were prepared for recording of isometric contractions in vitro. 2. After treatment with terbutaline in vivo, the response of the pilocarpine-contracted trachea to terbutaline and isoprenaline was slightly suppressed with no change in maximum relaxation. 3. After treatment with terbutaline in vivo the maximum depression of the incomplete tetanic contractions of the soleus muscle brought about by terbutaline or isoprenaline was diminished by about 70%. The response of the EDL was also attenuated after previous treatment with terbutaline in vivo. 4. These data indicate a selective development of tolerance to the effects of beta-adrenoceptor agonists in skeletal muscle as compared with tracheal smooth muscle. 5. The present results provide an experimental analogue to the clinical observation that patients being treated with beta-adrenoceptor agonists become tolerant to the tremorogenic rather than to the bronchodilating effect.     

HYPOTHALAMIC SUPERFUSION WITH HISTAMINE AGONISTS AND ANTAGONISTS MODIFIES THE PRESSOR RESPONSE TO HYPOTHALAMIC STIMULATION*

• 1 To investigate the effect of hypothalamic application of histamine agonists and antagonists on the pressor response to hypothalamic stimulation, the posterior hypothalamus of anaesthetized cats was superfused with drugs through a push-pull cannula and electrically stimulated with the non-insulated tip of the cannula.
• 2 Superfusion of the posterior hypothalamic area with histamine enhanced the pressor response to hypothalamic stimulation. The most pronounced effect of histamine was found, when the caudal region of the posterior hypothalamic area was superfused. The enhancing effect of histamine was abolished when the hypothalamus was pre-superfused with metiamide; it was slightly inhibited by pre-superfusion with mepyramine.
• 3 Dimaprit also enhanced the pressor response to hypothalamic stimulation; the effect of this drug was abolished by metiamide, whilst hypothalamic pre-superfusion with mepyramine was ineffective.
• 4 Superfusion of the hypothalamus with 2-methylhistamine did not change the pressor response to hypothalamic stimulation.
• 5 The enhancing effect of histamine was abolished by hypothalamic pre-superfusion with phentolamine, phenoxybenzamine or propranolol.
• 6 It is concluded that histamine enhances the pressor response to hypothalamic stimulation mainly by acting on H₂-receptors of the posterior hypothalamus. The inhibition of the effect of histamine by α-and β-adrenoreceptor blocking agents indicates the involvement of catecholaminergic systems of the hypothalamus.

     

DEGRANULATION OF RAT SALIVARY GLANDS FOLLOWING TREATMENT WITH RECEPTOR-SELECTIVE AGONISTS

1. The aim of this study was to find a drug that induces an almost complete degranulation of secretory cells in rat parotid and submandibular glands. 2. Phenylephrine (α-adrenergic), isoproterenol (β-adrenergic) and mecholine (muscarinic cholinergic) were tested. Time and degree of maximal depletion of acinar and granular convoluted tubule cells were determined morphologically. 3. Following phenylephrine-injection (5 mg/kg or 10.2 mg/kg, i.p.), no effect on the acinar granulation level was observed in either of the glands, while about 50–60% granular convoluted tubules were degranulated for at least 120–180 min post-injection. 4. With isoproterenol (5, 10, 40, 70 or 100 mg/kg, i.p.), degranulation of 100% of the acinar cells in the parotid and 80% of the acinar cells in the submandibular gland was observed 90 min post-injection. Granular convoluted tubule cells did not respond to this β-adrenergic drug. 5. Mecholine (3.75 or 7.5 mg/kg, i.p.) induced mainly degranulation of granular convoluted tubule cells (about 50% after 120 min). Numbers of granulated acinar cells decreased only slightly in both glands (about 10%, 90–120 min). 6. From this study it appears that with a relatively low dosage (5 mg/kg, i.p.) of isoproterenol, a high level of degranulation can be induced in acinar cells of rat parotid and submandibular glands without toxic side effects. Concerning granular convoluted tubules, only moderate degranulation was observed with phenylephrine and mecholine, respectively.     

THE CONTRACTILE RESPONSE OF SMOOTH MUSCLE TO IMMERSION IN HYPERTONIC SOLUTIONS

1. Strips of bovine tracheal muscle and rabbit aorta produced sustained contractions on perfusion with Krebs solution made twice normal strength by addition of sucrose. The contractures were relaxed on return to normal Krebs solution. 2. Similar contractures were produced by tracheal muscle strips in Krebs solutions made twice normal strength by addition of galactose, glucose or NaCl whereas urea caused only a transient contraction. 3. In twice normal strength Krebs solution (sucrose added) the basal tension of rat portal vein and guinea-pig taenia coli was increased. Spontaneous mechanical activity was maintained, but the frequency of contractions was reduced. 4. The hypertonic contracture of bovine trachea in twice normal strength Krebs solution (sucrose added) was reduced by 15% by omission of Ca from the bathing fluid (01 mmol/1 EGTA added). Severe Ca depeletion, by prolonged washing in Ca-free Krebs with 12.5 mmol/1 EGTA and Carbachol added, resulted in a 77% reduction in the hypertonic contracture. 5. In twice normal Krebs solution (sucrose added), the hypertonic contracture was partially relaxed by isoprenaline (4 × 10^?6 mol/1); the contractile response to carbachol was reduced; the contractile response to high-K Krebs solution was maintained. 6. Atropine (5 × 10^?7 mol/1) abolished the contractile response to carbachol, but had no effect on the hypertonic contracture. 7. It is suggested that the contraction of bovine tracheal strips in hypertonic solutions is mainly due to activation of the contractile myofilaments rather than simple cell shrinkage. Hypertonic solutions may also interfere with some steps in the excitation-contraction coupling sequence.     

COMPARISON OF THE ATTENUATING EFFECTS OF FOUR β-ADRENOCEPTOR AGONISTS ON RAT ISOLATED UTERUS AND AORTA

1. The ability of four 8-adrenoceptor agonists to attenuate oxytocin (0.2,2 and 20 nmol/L) or KCI (20,40 and 80 mmol/L)-induced Contractions of the uterus (n= 5–8 for each agonist) and the KCI (18 mmol/L)-induced contractions of the aorta (n = 9 for each agonist) from rats, pretreated with oestradiol has been compared. 2. Isoprenaline, salbutamol, terbutaline and procaterol (0.1–10μmol/L) attenuated the contractions of the uterus and the aorta. All four agonists had similar attenuating potencies on the uterus. 3. Procaterol caused the same maximal attenuation (33%) on the aorta as the other β-adrenoceptor agonists and is thus acting as a full β₂-adrenoceptor agonist under these experimental conditions. Isoprenaline and procaterol were much more potent than salbutamol and terbutaline in attenuating the aorta responses. 4. This study showed that isoprenaline and procaterol were potent attenuants on both the uterus and aorta whereas salbutamol and terbutaline were potent uterine but only modest aorta attenuants. This preliminary study indicates that the responsiveness of uterine and vascular tissue to certain β₂-adrenoceptors differs.     

MECHANISMS OF THE PRESSOR RESPONSE TO INTRAVENOUS THYROTROPIN-RELEASING HORMONE IN THE RAT

1. The purpose of this study was to examine the contribution of the sympatho-adrenomedullary system to the blood pressure response to an intravenous bolus of thyrotropin-releasing hormone (TRH) in conscious medullectomized and sham-operated rats. 2. The peak pressor effect of 0.5 mg TRH was significantly increased in rats having no adrenal medulla (+ 24.2 ± 1.6 mmHg, mean ± s.e.m., P<0.01) as compared to sham-operated animals (+12.2 ± 3.0 mmHg). 3. Blockade of alpha-adrenergic receptors with phentolamine abolished the pressor effect of TRH in control rats (+ 2.1 ± 1.9 mmHg) but did not attenuate the blood pressure response of medullectomized rats (+ 21.5 ± 4.7 mmHg). In contrast, beta-blockade with propranolol blunted the blood pressure responsiveness of rats subjected to adrenal medullectomy (+ 12.4 ± 2.6 mmHg) but did not modify the effect of TRH in sham-operated controls (+ 10.9 ± 2.9 mmHg). 4. The direct in vitro effect of TRH on isolated mesenteric rat arteries was also evaluated. TRH did not induce contractions of isolated arteries. 5. These results suggest that in rats with intact adrenals, the pressor effect of intravenous TRH is mediated primarily by a stimulation of alpha-adrenergic receptors. Adrenal medullectomy appears to enhance the blood pressure response to intravenous TRH. Activation of cardiac beta-adrenocep-tors seems to contribute to the blood pressure increasing effect of intravenous TRH in medullectomized animals.     

(±)-PINDOLOL HAS β2-ADRENOCEPTOR ANTAGONIST BUT NOT AGONIST ACTION ON THE COSTO-UTERINE MUSCLE OF THE RAT

1. The effects of isoprenaline and (+/-)-pindolol on rat isolated costo-uterine muscle have been compared. 2. Isoprenaline produced reproducible concentration-dependent inhibition of contractions, and maximal doses (less than 0.1 mumol/l) produced mean inhibition of 87, 94 and 97% of field, carbachol and potassium-stimulated preparations, respectively. 3. (+/-)-Pindolol, when effective, produced inhibition only in concentrations greater than its pA2 value (9.87) as an antagonist of isoprenaline; mean maximal effects were less than 60% of those produced by isoprenaline. 4. It is concluded that (+/-)-pindolol is a potent antagonist, but has only variable agonist action, at the beta 2-adrenoceptors of the rat costo-uterine muscle.     

THE INFLUENCE OF SUBACUTE DYFLOS ADMINISTRATION ON THE SENSITIVITY TO AGONISTS OF LONGITUDINAL AND CIRCULAR MUSCLE PREPARATIONS OF THE GUINEA-PIG ILEUM

1. Changes in the EC50 values to various agonists in longitudinal and circular muscle preparations of guinea-pig ileum were investigated following daily pretreatment of the animals for 10 days with dyflos (1.2 mg/kg, s.c.). 2. In the longitudinal muscle no significant change in sensitivity to acetylcholine and potassium chloride was noted following dyflos treatment. Marked subsensitivity to carbachol and histamine was observed. 3. In circular muscle a marked supersensitivity to acetylcholine occurred and there was no change in sensitivity to carbachol. 4. Dyflos treatment induced an increase in the slope of the log concentration-response curve and the maximal contractile response obtained to agonists in both longitudinal and circular muscle preparations. An increase in tissue mass was also associated with dyflos pretreatment. 5. Subsensitivity development was not attributable to changes in affinity for agonists at the receptor site but rather to changes at the post-receptor level leading to a nonspecific subsensitivity.     

THE NATURE OF THE PRESSOR RESPONSE TO CAROTID ARTERY OCCLUSION IN THE HEXAMETHONIUM-TREATED RAT

1. The blood pressure monitored from the cannulated right carotid artery and heart rate responses to occlusion of the intact left carotid artery were investigated in rats. 2. Hexamethonium abolished the response to ganglion stimulants but not that to carotid occlusion, although the time course and nature of the response were altered. 3. The pressor response to carotid occlusion in the presence of hexamethonium was not abolished by carotid sinus denervation, vagal section, tubocurarine, atropine, ethyl alcohol or an angiotensin II antagonist, but it was abolished by high doses of phenoxybenzamine. In six out of eight experiments the response was not abolished by cervical cord section. 4. It was concluded that the pressor response to carotid occlusion in the presence of hexamethonium in the rat involves an adrenergic mechanism which is at least in part independent of the autonomic ganglia, and which is mediated by an agent liberated from the brain, possibly under conditions of cerebral ischaemia.     

OPIATES INHIBIT THE DOPAMINERGIC ENHANCEMENT OF THE RENAL RESPONSE TO ALDOSTERONE IN THE RAT

1. Both naloxone, an opiate antagonist, and levorphanol, an opiate agonist, inhibit the enhanced renal response to aldosterone produced by both ?-dopa pretreatment and a high K⁺ diet. 2. This supports the evidence for a common mechanism of action for the enhancement of the renal response to aldosterone produced by ?-dopa and a high K⁺ diet. Whether this mechanism is dopaminergic or opiate is uncertain. 3. The inhibition of the enhanced response, produced by ?-dopa, by opiates is consistent with previous findings of displacement of ³H-dopamine from renal homo-genates by opiates and supports the hypothesis that the binding sites relate to the renal response to aldosterone.     

MICROPUNCTURE COMPARISON OF NEPHRON FUNCTION DURING ACUTE AND CHRONIC ADH EXCESS IN THE RAT

1. The aim of this study was to compare the effect of acute versus chronic ADH administration on the handling of sodium, potassium and water by the nephron. Simultaneous clearance and free-flow micropuncture experiments were performed on rats, infused with hypotonic Ringer solution, following either 1-3 h ('acute') or 10-12 days ('chronic') of continuous treatment with arginine vasopressin, 50 mU/h. A third group of animals receiving no exogenous ADH acted as controls. 2. Chronic ADH treatment led to more profound concentration of the urine and antidiuresis than acute treatment, due to enhanced extraction of water in the renal medulla. 3. Fractional sodium excretion during this protocol was increased after 'acute' but not 'chronic' ADH treatment. The acute natriuretic response was brought about principally along the length of the proximal tubule, probably due to volume expansion and increased arterial blood pressure. 4. Fractional excretion of potassium was also increased by 'acute' ADH, but this response was due to stimulation of potassium secretion in the late distal tubule. 5. It is concluded that acute and chronic exposure to ADH have different effects on nephron function, as a result of both direct and indirect actions.     

THE RELEVANCE OF THE RAT LUNG RESPONSE TO PARTICLE OVERLOAD FOR HUMAN RISK ASSESSMENT: A Workshop Consensus Report

On 23-24 March 1998, the International Life Sciences Institute (ILSI) Risk Science Institute convened a workshop entitled ''Relevance of the Rat Lung Response to Particle Overload for Human Risk Assessment. The workshop addressed the numerous study reports of lung tumors in rats resulting from chronic inhalation exposures to poorly soluble, nonfibrous particles of low acute toxicity and not directly genotoxic. These poorly soluble particles, indicated by the acronym PSPs (e.g., carbon black, coal dust, diesel soot, nonasbestiform talc, and titanium dioxide), elicit tumors in rats when deposition overwhelms the clearance mechanisms of the lung resulting in a condition referred to as ''overload. These PSPs have been shown not to induce tumors in mice and hamsters, and the available data in humans are consistently negative. The objectives were twofold: (1) to provide guidance for risk assessment on the interpretation of neoplastic and nonneoplastic responses of the rat lung to PSPs; and (2) to identify important data gaps in our understanding of the lung responses of rats and other species to PSPs. Utilizing the five critical reviews of relevant literature that follow herein and the combined expertise and experience of the 30 workshop participants, a number of questions were addressed. The consensus views of the workshop participants are presented in this report. Because it is still not known with certainty whether high lung burdens of PSPs     

EFFECT OF ETHAMSYLATE ON CARRAGEENAN-INDUCED RAT PAW OEDEMA: A COMPARISON WITH INDOMETHACIN

1. Ethamsylate (diethylammonium 2,5-dihydroxybenzene sulfonate, Dicynene), a systemic haemostatic agent with an unknown mechanism of action, was tested for anti-inflammatory activity using the carrageenan-induced rat paw oedema test. 2. Ethamsylate was shown to be an effective anti-inflammatory agent with a time course and amplitude of effect similar to that of indomethacin, although the potency was only about 4% of that for indomethacin. 3. When ethamsylate and indomethacin were co-administered they did not show additive effects, suggesting that they do not share a common mode of action. It is proposed that ethamsylate, like indomethacin, may inhibit prostaglandin synthesis. Ulceration produced by indomethacin, it is suggested that it may prove to be a useful addition to, or replacement for, indomethacin in the treatment of inflammatory disorders.     

REGIONAL VARIATION IN THE RESPONSE OF THE RAT VAS DEFERENS TO FIELD STIMULATION, TO NORADRENALINE AND TO TYRAMINE

SUMMARY 1. Experiments were performed with preparations obtained by medial transection of the rat vas deferens providing urethral and testicular segments, to determine whether the smooth muscle of this organ responds uniformly along its length to field excitation of sympathetic nerve terminals and to sympathomimetic amines. 2. Both preparations responded to pulses applied at 0.1 Hz with twitches which were blocked by guanethidine (1–10 μM) indicating that sympathetic nerve terminals were being stimulated. Xylazine (0.01–1 μM) also blocked the twitches. 3. In response to stimulation at 0.1 Hz the twitches of the urethral segment were larger but briefer than those of the testicular segment. However, the increase in tension with increase in stimulation frequency over the range 0.01–10 Hz was greater in the testicular than in the urethral segment. After a train of pulses at 1 Hz or above, the first few twitches of the testicular segment evoked by pulses applied at 0.1 Hz were facilitated, whereas twitches of the urethral segment were inhibited. 4. Noradrenaline (1–100 μM) and tyramine (1–100 μM) regularly enhanced twitches in response to stimulation at 0.1 Hz in the testicular segment but often reduced those in the urethral segment. Contractions in response to these amines occurred more regularly and were stronger in the testicular than in the urethral segment. The α-adrenoreceptor antagonists phenoxybenzamine (0.01 μM), phentolamine (10 μM) and thymoxamine (10 μM) blocked contractions and blocked or reversed the twitch enhancement produced by noradrenaline and tyramine. These observations indicate that the density of excitatory α-adrenoreceptors is greater at the testicular end of the tissue. 6. Twitch inhibition evoked by noradrenaline or by tyramine in urethral segments was resistant to blockade by phenoxybenzamine (0.01 μM), phentolamine 10 μM), thymoxamine (10μM) and propranolol (10 μM). 7. A histological comparison of the two ends of the vas deferens indicated that at the urethral end there was more circularly arranged muscle and that this interrupted bundles of longitudinally arranged muscle. The testicular end was thinner but had the higher proportion of longitudinally arranged fibres. 8. The differences between the two ends of the vas deferens in the arrangement of muscle layers and in the response to sympathetic nerve stimulation and to drugs may be of physiological significance in relation to the transport of sperm from the epididymis to the urethra.     

PLASMA RENIN RESPONSE TO ACUTE BLOCKADE OF ANGIOTENSIN II IN THE ANAESTHETIZED RAT

SUMMARY 1. Anaesthetized rats were infused intravenously for 1 h with a specific antagonist of angiotensin II, 1-Sar-8-Ala-angiotensin II (P-113), at a rate of 5 μ/kg per min, or with saline.
2. Blood samples were taken, before and after infusion, for measurement of plasma renin activity (PRA) and plasma renin concentration (PRC).
3. Saline infusion did not affect PRA or PRC.
4. Infusion of P-113 produced steep and highly significant increases in PRA (652%) and PRC (724%), despite a slight rise in mean arterial pressure.
5. Within 30 min of terminating P-113 infusion, PRA fell to 300%, and PRC to 278% of pre-infusion levels, and subsequently continued to fall.
6. It is suggested that the hypersecretion of renin produced by P-113 is due to blockade of the inhibitory control normally exerted by endogenous angiotensin II on renin release.     

EFFECTS OF DIFFERENT ANTISECRETORY DRUGS ON GASTRIC POTENTIAL DIFFERENCE IN THE RAT: COMPARISON WITH SUCRALFATE

The proton pump inhibitors omeprazole and lansoprazole and the histamine H₂receptor antagonists ranitidine and nizatidine were investigated for their effects on gastric transmucosal potential difference (PD) in the rat, in comparison with the gastroprotective compound sucralfate. Omeprazole (1–3 mg kg⁻¹, i.v.) and lansoprazole (1–3 mg kg⁻¹, i.v.) did not modify basal PD, but significantly reduced (by approx. 50–60%) the drop in PD caused by intragastric administration of acetylsalicylic acid (ASA, 60 mg kg⁻¹). Ranitidine (3–100 mg kg⁻¹, i.v.) and nizatidine (10–30 mg kg⁻¹, i.v.) behaved similarly to proton pump inhibitors, being ineffective on basal PD, while significantly reducing the effect of ASA. The antisecretory compounds did not change basal pH values. Sucralfate (0.5–1.5 g kg⁻¹intragastrically) caused a slight increase (approx. 20%) of basal PD and a dose-dependent reduction of ASA-induced fall in PD, with a maximum effect (65% reduction) comparable to that caused by the antisecretory agents. These results showed that ASA-induced disruption of the mucosal barrier can be reduced to the same extent by various antiulcer drugs, irrespective of their effects on gastric acid secretion.     

COMPARISON OF THE RESPONSE TO TOPICAL IRRITANTS IN HAIRLESS GUINEA PIGS AND HUMAN VOLUNTEERS

ABSTRACT

Small rodent laboratory animals lack the complex cutaneous structure and function of human skin, resulting in “all or none” responses to mild irritants so that the animals may show a less discriminative reaction pattern compared to human volunteers (HV). However, histological studies suggest that the skin of the hairless guinea pig (HLGP) is more similar to human skin than to the skin of haired guinea pigs and other rodents. We compared the tolerance pattern of six composite topical formulations with weak irritant potential in 20 human volunteers (HV) and in 15 male HLGPs. The skin care formulations (SCF), with and without either isopropyl palmitate, glycerol, canola oil, or (-)-α-bisabolol, were selected because they were known to cause a differentiated irritative response in HLGP. The HLGPs were treated twice a day on a 5 × 5 cm area on each flank with a SCF for four consecutive days. The irritant effects were quantified by clinical assessment, measurement of transepidermal water loss (TEWL), and colorimetry (a*-parameter). In humans the tolerability was evaluated clinically using the chamber scarification test. The ranking of the formulations was similar in the two models. However, HLGPs were statistically more sensitive to the formulations. Negative results in HLGPs are predictive of good tolerability in humans; however, positive results in the HLGPs do not necessarily indicate that a topical formulation cannot be used in humans.     

CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β2-MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT

1 Low concentrations of isoprenaline (EC₅₀= 45.6 nM) inhibited contractions in the isolated field stimulated rat vas deferens. This inhibitory effect was markedly attenuated by the postjunctional β₂-adreno-receptor antagonist timolol, but not affected by the prejunctional α₂ or postjunctional α₁-adrenoreceptor antagonists rauwolscine and prazosin, respectively. 2 In vas deferens of rats previously treated with reserpine, the postjunctional β₂-adrenoreceptor-mediated inhibitory response to isoprenaline was markedly potentiated. 3 High concentrations of isoprenaline (EC₅₀= 1.5 uM) also inhibited contractility in tissues in which postjunctional β₂-adrenoreceptors were maximally blocked by high concentrations of timolol. This contractile inhibition produced by isoprenaline was abolished by rauwolscine but not significantly altered by prazosin or pretreatment of the rats with reserpine indicating stimulation of prejunctional α₂-adreno-receptors. 4 Rauwolscine pretreatment unmasked an ability of isoprenaline (EC₅₀= 17.1 juM) to produce enhancement of field stimulation-induced contractions. This response was abolished by prazosin but was unaffected by timolol or reserpinization indicating an action upon postjunctional α₁-adrenoreceptors. 5 The data indicate isoprenaline activates adrenoreceptor mechanisms in the field stimulated rat vas deferens by a direct action not dependent upon endogenous catecholamines and with an order of activity of β₂>α₂>α₁. Pretreatment with reserpine produces rapid and selective development of supersensitivity to the postjunctional β₂-mediated inhibitory response of isoprenaline in this preparation.     

LACK OF EFFECT OF AGE ON THE CARDIOVASCULAR RESPONSE TO NEUROPEPTIDE Y INJECTION IN THE RAT NUCLEUS TRACTUS SOLITARIUS

1. Neuropeptide Y (NPY) is colocalized with catecholamines in central regions involved in blood pressure regulation and exerts depressor responses in the nucleus tractus solitarius (NTS). Ageing is accompanied by a decline in baroreflex function and a reduction in NPY concentrations in some brain areas. The present study investigated whether the cardiovascular response to NPY microinjection into the NTS and medullary NPY concentrations were conserved in aged rats. 2. Neuropeptide Y (6 pmol in 100 nL) unilaterally injected into the NTS of anaesthetized 3- or 17-month-old male Sprague-Dawley rats produced a prompt 9–10% fall in mean arterial pressure (MAP), which tended to last longer in aged rats. Decreases in heart rate (HR) observed following NPY administration into the NTS were modest but more prolonged than the depressor responses, ANOVA with repeated measures demonstrated no significant effect of age on the MAP or HR response to NPY injection into the NTS. Neuropeptide Y concentrations in the dorsomedial and ventrolateral medulla were not different between the two age groups. 3. Thus, the depressor and bradycardic responses to exogenous NPY administration in the NTS were maintained with age, in keeping with the observation of similar medullary NPY concentrations in adult and aged rats.