Effect of ATP on radiation damage to DNA caused by prolonged irradiation

The influence of bradykinin and kallikrein on the action of norepinephrine, epinephrine, isoprenaline, phentolamine, propranolol, aminophylline and theophylline on blood pressure was studied. The kinins potentiated the hypertensive action of norepinephrine and epinephrine, weakened the hypotensive action of isoprenaline, potentiated the hypotensive action of propranolol, and had no effect on the action of phentolamine, aminophylline and theophylline.     

Physiological changes in brushtail possums, Trichosurus vulpecula, transferred from the wild to captivity

The goal of the present study was to examine the interaction of cholecystokinin (CCK-33) and its fragments: C-terminal octapeptide (CCK-8) and C-terminal tetrapeptide (CCK-4) with alpha- and beta-adrenoceptor agonists and antagonists. The effect of this interaction on arterial blood pressure and function of isolated heart was studied in rats. The results indicate that: 1) CCK-33 enhances the influence of catecholamines: noradrenaline and isoprenaline, mainly on the function of isolated heart. This peptide does not change cardiovascular effects of alpha-adrenoceptor antagonist--phentolamine. CCK-33 diminishes the influence of propranolol on the function of isolated heart. The hypotensive effect of beta-adrenoceptor antagonist is not affected by CCK-33. 2) CCK-8 does not alter cardiovascular effects of noradrenaline and isoprenaline. The peptide diminishes the hypotensive effect of phentolamine and reverses the hypotensive effect of propranolol. CCK-8 enhances the influence of propranolol and does not change the influence of phentolamine on the function of isolated heart. CCK-8 enhances bradycardia evoked by propranolol. 3) CCK-4 does not change the influence of noradrenaline and isoprenaline on arterial blood pressure and diminishes the hypotensive effect of phentolamine and propranolol. The peptide does not change cardiac effects of noradrenaline and diminishes the effects of isoprenaline, phentolamine and propranolol. On the basis of the present study, we concluded that CCK-33 and its fragments CCK-8 and CCK-4 modify the cardiovascular action of alpha- and beta-adrenoceptor agonists and antagonists. We suggest that effects we have observed correlate with the activation of the CCK-A receptors (CCK-33, CCK-8) or CCK-B receptors (CCK-4). CCK-related peptides may increase or reduce the effects of catecholamines indirectly through activation of alpha-adrenoceptors. We can not exclude direct action of the peptides on the heart.     

Effects of dopamine on L-type Ca2+ current in single atrial and ventricular myocytes of the rat

1. The effects of dopamine on the L-type Ca2+ current (ICa,L) of both atrial and ventricular single myocytes and on the force of contraction of atrial trabeculae in rat heart were investigated. 2. Dopamine increased atrial ICa,L at concentrations higher than 1 microM, but had little or no effect on ICa,L at lower concentrations. The increase in ICa,L at high concentrations was reversed by propranolol and acetylcholine, but not by phentolamine. Activation and inactivation kinetics of ICa,L were not altered by dopamine. 3. In rat ventricular myocytes in which the D4 receptor mRNA does not express, dopamine (20-100 microM) also increased the ICa,L amplitude and propranolol reversed this effect. 4. Clozapine, a potent D4 receptor antagonist, blocked the augmenting effect of dopamine on ICa,L. However, this effect could be explained by beta-antagonism, since clozapine also inhibited the isoprenaline effect. 5. In the atrial trabeculae, the increase in contraction by dopamine (1 to 30 microM) was reversed by 1 microM propranolol, but not by 2 microM phentolamine. Low doses of dopamine (0.01 to 0.3 microM) did not affect the contraction in the controls or during a modest stimulation of the beta-adrenoceptor with 0.01 microM isoprenaline. 6. These results indicate that the positive inotropic action of dopamine is mediated through direct stimulation of the beta-adrenoceptor in both atrial and ventricular myocytes. Involvement of D4 receptor appears unlikely in the regulation of the atrial contraction.     

Mechanism of action of metoclopramide on opossum lower esophageal sphincter muscle

The purpose of this study was to investigate the mechanism of action of metoclopramide on the lower esophageal sphincter (LES) muscle of the opossum. Metoclopramide gave a dose-related increase in LES muscle active tension. A peak response of 12.5 +/- 2.1 g (mean +/- SEM) was achieved at 3.1 X 10(-4) M. The maximal and submaximal LES muscle response to metoclopramide could not be antagonized by atropine, hyoscine, hexamethonium, tetrodotoxin, phentolamine, diphenhydramine, or propranolol. Metoclopramide did not augment the submaximal muscle responses to gastrin I, acetylcholine, or norepinephrine. These studies suggest that in the opossum, metoclopramide acts through a direct action on the smooth muscle.     

Is sympathetic neurotransmission in the rat mesentery modulated by prejunctional beta adrenoceptors?

The influence of prejunctional beta adrenoceptors on neurotransmitter overflow from the sympathetic nerve terminals of the normotensive rat mesentery was investigated. The mesenteric vascular bed was isolated and perfused with Krebs-bicarbonate buffer containing phentolamine (10 microM), cocaine (10 microM) and corticosterone (40 microM). Periarterial nerve stimulation (2 Hz, 120 pulses) was performed at 8-min intervals. The influence of isoproterenol (ISO) on the stimulus-induced fractional overflow of norepinephrine (S-I OFLO) was determined by generating concentration-effect curves (0.1-1000 nM, 3- or 6.5-min exposure to each concentration). ISO did not significantly increase S-I OFLO at any concentration. On the contrary, there was a decrease in S-I OFLO at the highest concentration of ISO (1 microM). The time course of the actions of ISO was studied by utilizing single concentrations of ISO (10 nM or 1 microM, 6.5-min exposure). The presence of ISO did not significantly affect S-I OFLO at either concentration. However, S-I OFLO was decreased during stimulation periods after the removal of ISO (1 microM) from the perfusate. This inhibition was significantly attenuated by propranolol (1 microM). Pretreatment with the cyclooxygenase inhibitor indomethacin (2.8 microM) had no effect on the response to ISO or the inhibition observed after ISO removal. This inhibition remained sensitive to blockade by propranolol. Salbutamol (100 nM, 6.5-min exposure), a preferential beta 2 adrenoceptor agonist, did not facilitate or inhibit S-I OFLO. These data suggest that facilitatory prejunctional beta adrenoceptors are either not present or weakly coupled to their effector system in the normotensive rat mesentery.(ABSTRACT TRUNCATED AT 250 WORDS)     

CNS regulation of blood lactate concentration in anesthetized rats

This study evaluated the effect of stimulating the central nervous system (CNS) with neostigmine, an inhibitor of acetylcholinesterase, on the blood lactate concentration in fed rats and in rats fasted for 48 hours. After the rat was anesthetized with pentobarbital, neostigmine was stereotaxically injected into the third cerebral ventricle. In fed rats, the central injection of neostigmine significantly increased the blood lactate level, while concomitantly increasing plasma glucagon, epinephrine and norepinephrine concentrations. Constant infusion of somatostatin throughout the experiments, to inhibit glucagon secretion from the pancreas, did not affect alterations in blood lactate by central injection of neostigmine. In adreno-medullated rats, CNS-stimulation by neostigmine still increased plasma norepinephrine significantly, however, the alteration in blood lactate was only one-third of that in intact rats. Intraperitoneal propranolol, but not phentolamine, prevented the rise in lactate. Neostigmine increased lactate in fasted rats as well as in fed rats. We conclude that in anesthetized rats, stimulation of the CNS by neostigmine increases blood lactate mainly through circulating epinephrine and partially through circulating norepinephrine or direct sympathetic nervous stimulation; glucagon does not appear to be involved in the increase in blood lactate.     

Gel isoelectric focusing of human-serum transferrin

Prazosin is a quinazoline that has a long lasting hypotensive effect. To investigate the mechanisms underlying its action experiments were performed in 75 dogs anesthetized with pentobarbitone sodium. Prazosin, after i.v. injection, lowered arterial pressure without altering heart rate and venous pressure, and decreased pressor responses to epinephrine, norepinephrine and splanchnic nerve stimulation. Orthocarboxybenzeno-seleninic acid, an alpha-adrenoceptor blocker, antagonized the hypotensive effect of prazosin. Neither administration of propranolol nor carotid sinus local anesthesia impaired prazosin hypotensive effects. Topical application of prazosin on both carotid sinuses had no effect on general arterial blood pressure; after intravenous administration it did not change the hypotension caused by electrical stimulation of the carotid sinuses. The depressor effects of papaverine and sodium nitrite on blood pressure were enhanced by prazosin. It is concluded that this drug exerts its hypotensive effect by blocking, alpha-adrenoceptors and by possibly relaxing vascular smooth muscle.     

Hormonal regulation of heparin secretion by rat mast cells during stress

Administration of non-selective beta-blocker propranolol prevented the stress-activated action whereas the alpha-agonist isoprenaline enhanced the effect of immobilisation stress on the rat mast cells. beta-antagonists or agonists exerted no effect on the heparine secretion by the mast cells. ACTH activated the secretion in the absence of stress.     

Evidence that phentolamine is not an inhibitor of extraneuronal uptake

1. Tracheal segments from guinea-pigs pretreated with 6-hydroxydopamine were incubated in isoprenaline at 37 degrees C for 5 min in the absence or presence of phentolamine. Catechol-O-methyl transferase was inhibited by 100 mumol l-1 U-0521. Tissues were prepared for fluorescence histochemistry and accumulated isoprenaline in trachealis smooth muscle cells (fluorescence) was measured by microphotometry. 2. Phentolamine, in concentrations up to 100 mumol l-1, had no effect on isoprenaline fluorescence. 3. It is concluded that phentolamine does not inhibit extraneuronal uptake in concentrations used to block alpha-adrenoceptors in isolated tissue experiments. Thus, is can be present in experiments designed to examine the effects of extraneuronal uptake inhibitor drugs on beta-adrenoceptor-mediated responses.     

Effect of adrenergic blocing agents on peripheral noradrenaline induced thermoregulatory responses in the pigeon at heat

1. The hyperthermic effect of intramuscular NA at 32 degrees C was abolished by propranolol but not by phentolamine preinjection. 2. The lack of hyperthermic response was at least partly due to the blocking effect of propranolol on beta-receptor mediated in heart rate. 3. After NA the respiratory rate was gradually increased in birds preinjected either with propranolol or with phentolamine.     

Effect of fibrinogen degradation products on the rat blood vessels

Effect of fibrinogen degradation products on the rat blood vessels. Acta Physiol. Pol. 1977, 28 (2): 153--159. It was found that fibrinogen degradation products (FDP) exert a slight hypotensive effect and increase the flow of Tyrode's solution through isolated hindpaw of rat. The investigated peptides failed to change significantly the action of noradrenaline and had an additive effect with isoprenaline. Propranolol reduced the effects of FDP and isoprenaline. It is suggested that the described effects may be due to stimulation of the vascular beta-adrenergic receptors by FDP.     

Effects of bradykinin on [3H]-norepinephrine release in rat hypothalamus

1. We examined the regulatory actions of bradykinin on norepinephrine release in the hypothalamus of rats. 2. Bradykinin increased the stimulation-evoked [3H]-norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner (1 Hz: S2/S1 ratio, mean +/- s.e.m., control 0.868 +/- 0.016, n = 6; bradykinin 1 x 10(-6) mol/L 1.039 +/- 0.018, n = 6, P < 0.05; bradykinin 3.3 x 10(-6) mol/L 1.130 +/- 0.064, n = 6, P < 0.05). The basal release of [3H]-norepinephrine was not affected by the peptide. 3. Bay K 8644, a dihydropyridine-sensitive calcium channel agonist, significantly potentiated the facilitatory effect of bradykinin on norepinephrine release, although Bay K 8644 by itself had no significant effect. By contrast, nicardipine, a dihydropyridine-sensitive calcium channel blocker, reversed the increase in norepinephrine release induced by bradykinin and Bay K 8644. 4. These results indicate that bradykinin may increase norepinephrine release in rat hypothalamus, partially mediated by interactions with dihydropyridine-sensitive calcium channels.     

Epinephrine facilitates cardiac fibrillation by shortening action potential refractoriness

Epinephrine released during ventricular tachycardia (VT) or early fibrillation (VF) appears to be instrumental in stabilizing fibrillation. However, mechanisms remain unclear. Effects of epinephrine on refractory period at normal sinus rates depend on basic cycle length, but effects at short cycle lengths, typical of VT/VF, are unknown. Therefore, the goal of this study was to determine whether epinephrine shortens action potential duration and refractoriness at these short cycle lengths. To simulate early VT/VF, myocardial cell aggregates (n = 35) were paced using field stimulation (5 ms rectangular waveform) at cycle lengths of 200, 180, 160 and 140 ms, which occur during in situ fibrillation: normal sinus rhythm was simulated by pacing at 600 and 400 ms intervals. Action potentials and excitation threshold were recorded with intracellular microelectrodes under control conditions, with 0.9 microM/l epinephrine, and with 0.9 microM/l epinephrine and 0.5 microM/l propranolol. At short cycle lengths, epinephrine significantly shortened action potential duration and refractoriness compared to control. At a cycle length of 160 ms, action potential duration was reduced by 14 ms at 60% repolarization (P < 0.0002) and stimulation threshold by 18% (P < 0.02). Epinephrine also allowed pacing at a cycle length of 140 ms, not achievable under control conditions. Because epinephrine decreases action potential duration at short cycle length in situ, re-entry wavefronts are less likely to encounter refractory tissue: fibrillation is more likely to occur and to remain stabilised. Reduction in action potential duration and excitation threshold were reversed by propranolol, suggesting that epinephrine effects are produced by beta-stimulation.     

Impairment of vasodilator function in basilar arteries from aged rats

BACKGROUND AND PURPOSE: Aging is associated with a reduction in cerebral perfusion. Impaired vasodilatation in large brain arteries could be implicated. This study sought age-related changes in vasodilator responses to norepinephrine in rat basilar artery and investigated which aspects of norepinephrine's action are responsible. To study the effect of aging per se, we used the rat, an animal with resistance to development of age-related pathologies. METHODS: Vascular responses were studied in basilar arteries from young (3 to 4 months old) and old (20 to 22 months old) normotensive Sprague-Dawley rats with wire myography. Endothelial structure was assessed with confocal microscopy. RESULTS: There was no age-related difference in blood pressure and in KCl or 5-hydroxytryptamine (5-HT) contractions. Relaxation to bradykinin or its absence predicted an intact or denuded endothelium, confirmed by confocal microscopy. Norepinephrine produced concentration-dependent relaxation that was significantly smaller in old rats, with or without endothelium. This response was significantly smaller in endothelium-denuded vessels, or after preincubation with NG-nitro-L-arginine methyl ester or propranolol, but not with rauwolscine. CONCLUSIONS: In old and young rats the vasodilator action of norepinephrine in basilar artery is dependent on beta-adrenoceptors and nitric oxide. The impaired vasodilatation to norepinephrine found in the basilar artery from old rats might be caused by (1) a reduction in nitric oxide production and/or release or (2) beta-adrenoceptor alteration at the endothelium and/or the vascular smooth muscle. This impairment of vasodilator function can be ascribed to the aging process per se and not to other age-related alterations, such as hypertension.     

Effect of norepinephrinergic system on ipalbidine analgesia

Ipalbidine (Ipa) is a photoactive alkaloid isolated from the seeds of ipomoea hardwickki Hemsl. The analgesic effects of Ipa were determined by rat tail flick method. A dose-dependent analgesic effect was found after s.c. or i.c.v. administration of Ipa, but no analgesia was observed after intrathecal injection, indicating that the analgesic effect of Ipa is central in origin, and it acts mainly on supraspinal substrate. The analgesic effect induced by Ipa (60 mg.kg-1, s.c.) was markedly reduced by reserpine (2 mg.kg-1, i.p.) given 24 h before Ipa, which was reversed by combined administration with i.c.v. norepinephrine (NE). In addition, Ipa-induced analgesia was significantly attenuated by electrolytic lesion of bilateral destruction of locus coeruleus, and combined administration with diethyldithiocarbamate (200 mg.kg-1, i.p.), phentolamine (10 mg.kg-1, i.p. or i.c.v.), and prazosin (3 mg.kg-1, s.c.). But no influence was observed on the analgesia of Ipa after administration of yohimbine (5 mg.kg-1, s.c.) or propranolol (10 mg.kg-1, i.p.). These results suggest that the analgesia caused by Ipa is closely related to the function of the central norepinephrinergic system, and probably mediated by indirectly acting on alpha 1 receptors, but not alpha 2 or beta receptors.     

Percutaneous endoscopic gastrostomy: state of the art, 1998

BDF 9148, a positive cardiac inotrope, relaxes the rat isolated portal vein and the KCl-contracted rat aorta. The aims of our study were to determine the mechanism of action of BDF 9148, and to ascertain whether the relaxing effect of BDF 9148 was maintained in the presence of the hypertrophy associated with hypertension, by investigating the effects of BDF 9148 on the contractility and electrophysiology of aortae of Wistar Kyoto normo-tensive rats (WKY) and Spontaneously Hypertensive Rats (SHRs). High concentrations of veratridine contracted the quiescent rat aorta. BDF 9148 had no effect on the quiescent, but relaxed the KCl-contracted WKY and SHR aorta by a tetrodotoxin insensitive mechanism, and these relaxations decreased with age but were not greatly altered by hypertrophy. The verapamil relaxations of the KCl-contracted aorta were not altered by age or hypertrophy. The ability of KCl to depolarise the aorta was reversed by verapamil, but not by BDF 9148. On the contracted rat aorta, the relaxant responses to acetylcholine were abolished by removal of the endothelium but potentiated by IBMX (10[-6] M), and the responses to isoprenaline were inhibited by propranolol (10[-6] M) but potentiated by forskolin (10[-7] M). The relaxation responses of the KCl-contracted aorta to BDF 9148 were not altered by removal of the endothelium, or by propranolol, forskolin and IBMX. In summary, the effects of verapamil and BDF 9148 on the aorta are different, and thus it is unlikely that the relaxant responses to BDF 9148 on the aorta are due to calcium channel blocking activity. The mechanism of the relaxant effect of BDF 9148 on the aorta remains unknown, but we have shown the response is endothelium-independent, and not mediated by sodium channel opening, hyperpolarization, beta-adrenoceptors, or by stimulating adenylate cyclase or guanylate cyclase.     

Effects of alpha- and beta-adrenoceptor blockade on purine secretion induced by sympathetic nerve stimulation in the rat kidney

To characterize the effects of renal sympathetic nerve activation (RSNA) on renal purine secretion, 13 perfused rat kidneys were stimulated with periarterial electrodes at 7 Hz for 3 min, and purine secretion was determined by measuring with high-performance liquid chromatography purines in the renal venous perfusate 1 min before and during the last minute of RSNA. RSNA significantly increased renal perfusion pressure and significantly increased the secretion of adenosine and adenosine metabolites (inosine, hypoxanthine, and xanthine) by 2- to 5-fold. To investigate the participation of alpha- and beta-adrenoceptors in this response, four groups of perfused kidneys (n = 5/group) were pretreated with either vehicle, prazosin (alpha1-adrenoceptor antagonist; 0.03 microM), phentolamine (alpha1/2-adrenoceptor antagonist; 3 microM), or propranolol (beta1/2-adrenoceptor antagonist; 0.1 microM), and purine secretion was measured before and during RSNA at 1, 3, 5, 7, and 9 Hz. Prazosin, phentolamine, and propranolol abolished the RSNA-induced increase in the secretion of adenosine, inosine, hypoxanthine, and xanthine. In contrast, prazosin and phentolamine nearly abolished, whereas propranolol only slightly reduced, renal vascular responses to RSNA. Our results indicate that RSNA increases renal purine secretion via a mechanism that requires both alpha- and beta-adrenoceptors. It is well known that in the kidney adenosine activates renal afferent nerves, enhances renovascular responses to norepinephrine and angiotensin II, and increases sodium reabsorption; therefore, RSNA-induced adenosine production may contribute to the hypertensive effects of RSNA. Moreover, the antihypertensive effects of beta-adrenoceptor antagonists may in part be due to inhibition of RSNA-induced renal adenosine production.     

A trial of the synthetic malaria vaccine SPf66 in Tanzania: rationale and design

By using acetyl strophanthidin (AS) 0.2 mumol/L, the delayed after-depolarization (DAD) was induced in sheep cardiac Purkinje fibers and recorded with intra-cellular microelectrode. When beta-adrenoceptor was blocked by propranolol 1.0 mumol/L, phenylephrine 1.0 mumol/L increased the amplitude of DAD from 8.1 +/- 2.2 mV to 9.5 +/- 2.8 mV, prolonged the duration of DAD from 240 +/- 47 ms to 273 +/- 47 ms (n = 13, P < 0.01) and increased the up rising velocity of DAD from 0.039 +/- 0.023 V/s to 0.051 +/- 0.026 V/s (n = 13, P < 0.05). The DAD occurred earlier for 30 +/- 47 ms to preceding action potential (n = 13, P < 0.05). When triggered action potentials were induced by norepinephrine 1.0 mumol/L on the basis of DAD, propranolol 1.0 mumol/L could suppress the triggered beats while phentolamine 1.8 mumol/L showed little effect. The above results indicate that excitation of alpha-receptor had only slight augmentation effect on DAD. However, for the triggered activity induced by DAD, the inhibitory effect of beta-blockers are stronger than that of alpha-blockers.     

Bradykinin B2-receptor-mediated stimulation of exocytotic noradrenaline release from cardiac sympathetic neurons

Myocardial ischemia, as well as angiotensin-converting-enzyme-inhibitors, increase cardiac concentrations of the non-apeptide bradykinin. Cardiac effects of bradykinin are potentially mediated by modulation of sympathoadrenergic neurotransmission. Accordingly, the present study was designed to examine the influence of bradykinin on exocytotic noradrenaline release from rat isolated perfused heart. Exocytotic noradrenaline release was induced by electrical field stimulation (1 min, 5 V, 6 Hz) twice to compare the effect of intervention (S2) with respective control stimulation (S1). The overflow of endogenous noradrenaline was determined by high pressure liquid chromatography and electrochemical detection. The results are expressed as the mean S2/S1 ratio+/-S.E.M. Bradykinin (1 micromol/l) evoked a significant increase in noradrenaline release (S2/S1: 1.60+/-0.12; P<0.01), which was even more pronounced after inhibition of neuronal reuptake of noradrenaline by desipramine (0.1 micromol/l: S2/S1: 1.83+/-0.15; P<0.01) excluding interference of bradykinin with the noradrenaline uptake1 carrier. The concentration-response curve for bradykinin (0.1 nmol/l to 10 micromol/l) revealed a maximum effect at 1 micromol/l and an EC50-value of 7.5 nmol/l. The effect of bradykinin was unaltered by the B1-receptor antagonist des-Arg9 (Leu8)-bradykinin (1 micromol/l; S2/S1: 1.69+/-0.17), whereas it was reduced significantly by the B2-receptor antagonist Hoe 140 (1 micromol/l; S2/S1: 1.14+/-0.11; P<0.05). Des-Arg9-bradykinin (1 micromol/l), a specific B1-agonist, had no effect on stimulation-induced noradrenaline release (S2/S1: 0.94+/-0.08). Utilizing pharmacological interventions, we attempted to characterize the intraneuronal signal transduction pathway mediating the effect of bradykinin on exocytosis. Neither inhibition of cyclooxygenase nor blockade of nitric oxide synthesis affected bradykinin-induced stimulation of noradrenaline release. Likewise, inhibition of protein kinase C by bisindolylmaleimide (1 micromol/l) or tyrosine kinase by genistein (10 micromol/l) had no effect on the promoting action of bradykinin. In contrast, inhibition of cytosolic phospholipase A2 activity by the specific inhibitor AACOCF3 (1 micromol/l) prevented bradykinin-induced increase in noradrenaline release (S2/S1: 1.09+/-0.15; P<0.01). In conclusion, bradykinin increases exocytotic release of endogenous noradrenaline from cardiac sympathetic neurons via activation of presynaptic B2-receptors. Intraneuronal coupling of B2-receptors to phospholipase A2 appears to mediate the facilitatory effect of bradykinin on noradrenaline release in rat heart.     

Apoptosis in the male gonad

1. Previous work has shown that enalaprilat, an inhibitor of angiotensin-converting enzyme (ACE), potentiated the actions of alpha 1-adrenoceptor antagonists; it was hypothesized that angiotensin II (AngII) modulated the activity of alpha 1-adrenoceptors. This hypothesis was tested in Sprague-Dawley rat isolated perfused tail arteries using the AT1 receptor antagonist losartan and the AT2 receptor antagonist PD123319. 2. Losartan had no alpha 1-adrenoceptor antagonist effects at concentrations below 1 mumol/L. Similarly, losartan (0.1 mumol/L) had no effect on the alpha 1-adrenoceptor antagonist action of doxazosin (1, 10 nmol/L) nor on the potentiation of doxazosin by enalaprilat (1 mumol/L). 3. PD123319 (0.1 mumol/L) had no alpha 1-adrenoceptor antagonist effect but altered the mode of action of the alpha 1-adrenoceptor antagonist doxazosin: PD123319 changed doxazosin from a competitive to a non-competitive antagonist, as evidenced by the reduced slope of the dose-response curve for the alpha 1-adrenoceptor agonist phenylephrine. 4. These results suggest that AngII can modulate alpha 1-adrenoceptor function in rat tail arteries via an indirect action at AT2 receptors. However, the present results do not rule out the involvement of bradykinin, endothelin or prostaglandin in the modulation of alpha 1-adrenoceptor function by angiotensin II.