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1. The present study was carried out to determine whether rilmenidine, a recently introduced antihypertensive agent which acts on alpha 2-adrenoceptors, has partial agonist activity on prejunctional alpha 2-adrenoceptors in guinea-pig atria. 2. Isolated preparations of guinea-pig atria were incubated with [3H]-noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as an index of release of transmitter noradrenaline. 3. Rilmenidine (1 mumol/l) inhibited noradrenaline release evoked by short trains (five, 20 and 50 pulses) of sympathetic nerve stimulation and this inhibitory effect of rilmenidine was antagonized by the alpha 2-adrenoceptor antagonists, idazoxan (0.1 and 0.3 mumol/l) and rauwolscine (0.3 mumol/l) whereas it was not affected by the alpha 1-adrenoceptor antagonist prazosin (0.1 mumol/l). 4. On the other hand, rilmenidine (1 mumol/l) enhanced noradrenaline release evoked by long trains (150 and 300 pulses) of stimulation and this effect was also abolished by idazoxan (0.1 mumol/l). 5. These findings suggest that the effects of rilmenidine on transmitter release depend on the degree of auto-inhibition: when the concentration of noradrenaline in the biophase of the prejunctional alpha 2-adrenoceptors is low, rilmenidine acts as an agonist, but when the concentration is high it acts as an antagonist. Thus, rilmenidine, like clonidine, is a partial agonist on prejunctional alpha 2-adrenoceptors in guinea-pig atria.

1. Isolated preparations of rat anococcygeus muscle were incubated with [3H]-noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as a measure of release of transmitter noradrenaline. Isometric contractile responses were also measured. 2. Angiotensin I (0.03 microM) and angiotensin II (0.03 microM) produced non-sustained contractile responses and enhanced the stimulation-induced (S-I) effluxes of radioactivity as well as the contractile responses to electrical stimulation. These effects were blocked by the angiotensin II receptor antagonist saralasin (0.03 microM), and the effect of angiotensin I, but not angiotensin II, was blocked by the angiotensin converting enzyme inhibitor captopril (0.1 microm). 3. The findings indicate that there are both pre- and postjunctional receptors for angiotensin II and that angiotensin I is converted to angiotensin II in the anococcygeus muscle preparation. 4. Isoprenaline (0.1 microM) slightly enhanced the S-I efflux of radioactivity, and produced a greater enhancement after neuronal uptake blockade with desipramine (0.03 microm) and alpha-adrenoceptor blockade with phentolamine (1 microM). 5. The facilitatory effect of isoprenaline on S-I efflux of radioactivity was abolished by propranolol (0.3 microM), but was not affected by low concentrations of saralasin (0.03 microM) or captopril (0.1 microM) which abolished the effect of angiotensin I. The findings suggest that isoprenaline acts directly on prejunctional beta-adrenoceptors to enhance S-I noradrenaline release, rather than indirectly by releasing angiotensin II from within the tissue. Higher concentrations of saralasin (0.1 microM) or captopril (5 microM) did block the facilitatory effect of isoprenaline. The significance of this finding is not clear.

Studies were carried out to determine whether rilmenidine, a recently introduced antihypertensive agent with a similar mechanism of action of clonidine, possesses histamine-like activity on tissues responding to histamine H2-receptor agonists. In guinea-pig isolated atria, both histamine and clonidine caused concentration-dependent positive chronotropic effects which were blocked by the histamine H2-receptor antagonist cimetidine (5 microM); in contrast, rilmenidine produced a concentration-dependent negative chronotropic effect which was not altered by cimetidine. In stilboestrol-treated rat isolated uterus contracted by KCl, histamine and clonidine produces concentration-dependent relaxations which were blocked by cimetidine (5 microM); rilmenidine also produced relaxation, but this was not affected by cimetidine (5 microM). These findings suggest that rilmenidine, unlike clonidine, does not activate histamine H2-receptors in either guinea-pig atria or rat uterus.

The Tripterygium wilfordii (TW) was used to treat experimental allergic encephalomyelitis (EAE) in guinea-pig. The morphological change was observed by using light microscope. Lymphocytic histochemical staining was performed on the spinal cord from EAE in guinea-pig. The results were: The incidence of inflammatory reaction, neuraxial swelling, break and neuronal necrosis in the treatment group was lower than that in the control group (P less than 0.01-0.005); the variation of incidence of neurofibrillar demyelinating in the treatment group was smaller than that in the control group (P less than 0.025). The result of ANAE and ALP staining for lymphocytes in the spinal cord from EAE was T-cell. It showed TW could inhibit the allergic action and decrease tissular injury.

The muscarinic agonist McN-A-343 did not affect the tone or nitroprusside-induced relaxations of the rat anococcygeus, but inhibited non-adrenergic non-cholinergic (NANC) relaxations. Atropine, pirenzepine and gallamine blocked the McN-A-343 inhibition of NANC relaxations. Agonists of alpha 1-(methoxamine) or alpha 2-adrenoceptors (clonidine, rilmenidine) increased tone and reduced NANC relaxations. Carbachol also increased tone but produced a greater reduction of NANC relaxations. The findings suggest that activation of prejunctional muscarinic receptors on NANC terminals inhibits transmitter release, but there is no evidence for prejunctional alpha-adrenoceptors.

We have given whole blood as one of the main constituents of burn shock resuscitation for the past 28 years. To appraise the value of using whole blood, we have summarized the clinical experience of 2630 burn patients. Overall mortality was 4.18%. The lethal area of the burn were 50% of the population is expected to die was 82.8% total body surface area and 57.4% third-degree burns. The incidence of renal failure, pulmonary edema, and gastrointestinal bleeding was 0.9%, 0.4%, and 0.6% respectively. To confirm the advantage of transfusion of whole blood, we have carried out a series of experimental studies. Two groups of 25 dogs with 25% total body surface area full-thickness burns were treated with two resuscitation regimens. Group I was treated with whole blood, and group II with no blood, during the shock phase. After 48 hours, the infusions were stopped. Measurements were made before the burn and 2, 24, 48, 72, and 144 hours after the burn injury. The animals were then killed for histologic studies. From our data, we concluded that whole blood used in burn shock did not increase hemoconcentration or viscosity; it improved anemia, oncotic pressure, hypoproteinemia, acid-base balance, oxygenation, hemodynamics, and myocardial contractility, promoted cardionatrin secretion, reduced edema of tissue, and protected viscera from degenerative changes and bacterial colonization.

1. The nitric oxide (NO) synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA), but not D-NMMA, inhibited the NANC-mediated relaxations of the rat anococcygeus muscle, but did not affect the relaxation produced by sodium nitroprusside. 2. The inhibitory effect of L-NMMA was reversed by L-arginine but not by D-arginine, and prior exposure to L-arginine blocked the effect of L-NMMA. 3. The noradrenergically mediated contractions of the anococcygeus elicited by field stimulation were slightly enhanced by L-NMMA, but the response to noradrenaline was not affected. 4. The results suggest that NANC transmission in the rat anococcygeus muscle involves the generation of NO from arginine.