Changes in splenic diameter measured by sonomicrometry in response to various adrenergic stimulants were estimated together with simultaneously measured arterial haemoglobin content (HGB) and haematocrit (HCT) in anaesthetized dogs. Splenic diameter decreased following intravenous injections (i.v.) of adrenaline, noradrenaline and phenylephrine and splenic nerve stimulation associated with increases in arterial HGB and HCT, which were significantly attenuated by prazosin i.v. After prazosin i.v., adrenaline i.v. increased splenic diameter significantly, but noradrenaline i.v. did not. Isoprenaline i.v. increased splenic diameter transiently, followed by a decrease that was abolished by prazosin i.v. During occlusion of splenic arteries and veins, adrenaline i.v. and phenylephrine i.v. did not cause any change in arterial HGB and HCT. Injection to splenic artery (i.a.) of phenylephrine induced a significant decrease in splenic diameter that was attenuated by prazosin i.a. but not by yohimbine i.a. Clonidine i.a. did not change splenic diameter. The present results indicate that splenic contraction, which is mediated through alpha 1-adrenoceptor activation, causes a significant increase in arterial HGB and HCT.

1. Responses of splenic diameter measured by sonomicrometry to alpha- and beta-adrenoceptor stimulants were estimated together with simultaneously measured systemic arterial and splenic venous concentrations of red blood cells (RBC), white blood cells (WBC) and platelets (PLT) in anaesthetized dogs. 2. Intravenous and intrasplenic arterial injections of adrenaline, noradrenaline and phenylephrine all produced profound decreases in splenic diameter. Increases in systemic arterial concentrations of RBC produced by these stimulants were observed immediately following the splenic contraction and marked increases in splenic venous concentration of RBC. 3. Adrenaline and noradrenaline both caused rapid and transient decreases in WBC release from the spleen and these agonists then, in addition to phenylephrine, caused gradual and small increases in systemic arterial WBC concentrations. The increases in arterial RBC and WBC concentrations were abolished by transient isolation of the spleen from the systemic circulation. These three agents did not significantly modify differences between splenic venous and systemic arterial concentrations of PLT. 4. Intra-arterial injections of isoprenaline caused an increase in splenic diameter and a significant decrease in the splenic venous concentration of WBC, but barely influenced the veno-arterial differences in RBC and PLT concentrations across the spleen. 5. The present results indicate that contraction of the spleen through stimulation of splenic alpha1-adrenoceptors contributes to supplying RBC but not PLT into the systemic circulation, whereas splenic beta-adrenoceptor activation leads to splenic dilatation with increased sequestration of WBC to the spleen despite no changes in the release of RBC and PLT from the spleen.

1 Platelet-activating factor (PAF) is a phospholipid mediator with potent cardiovascular and haematological actions. But its mechanisms of action in vivo have not been fully elucidated, probably due to difficulties arising from previous findings that the effects of PAF are largely mediated by the release of a variety of other autacoids. In the present study, the roles of nitric oxide and eicosanoids in the effects of PAF (0.01 -0.25 pg kg-1 i.v.) on systemic and pulmonary vasculatures and circulating blood cell count were pharmacologically evaluated in anaesthetized dogs. 2 Higher doses of PAF (>0.1 yg kg-1) produced a biphasic systemic hypotension. The first hypotension seen 30 s after the injection was accompanied by a decrease in systemic vascular resistance, thrombocytopenia and leukopenia, while the second hypotension seen 1-2 min after PAF was accompanied by a marked rise in pulmonary vascular resistance and decreases in aortic blood flow and cardiac contractility. Lower doses of PAF (0.01-0.05 Mg kg-') caused only the first responses in a dosedependent manner. 3 Pretreatment with indomethacin inhibited the second responses to PAF without affecting the first responses. The thromboxane A2/prostaglandin H2 (TP)-receptor antagonist vapiprost blocked the PAFinduced rise in pulmonary vascular resistance. AA-861, a 5-lipoxygenase inhibitor, attenuated the PAFinduced cardiac depression. The nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester inhibited the PAF-induced early decrease in systemic vascular resistance. 4 All observed changes in haemodynamics and blood cell count after PAF were almost abolished by TCV-309, a PAF-receptor antagonist. 5 Reproducible hypotension and thrombocytopenia produced by a lower dose of PAF (0.05 Mg kg-1) were respectively attenuated and potentiated by pretreatment with NG-nitro-L-arginine, another nitric oxide synthase inhibitor. Administration of L-arginine reversed the effects of the nitric oxide synthase inhibitor. 6 These results indicate that PAF-receptor-mediated production of not only eicosanoids but also nitric oxide may contribute to the cardiovascular and haematological responses to PAF in the dog.

1. The effect of vasodilators on spleen volume and the blood storage function is not yet well elucidated. To this end, in the present study the effects of prostacyclin, a potent vasodilator, on splenic diameter and blood cell concentrations in arterial and splenic venous blood were evaluated in anaesthetized dogs. 2. The main splenic artery and vein were dissected for measurement of splenic arterial blood flow and intra-arterial administration and for sampling of splenic venous blood, respectively. The diameter of the spleen was measured continuously by sonomicrometry. Counts of white blood cells (WBC), red blood cells (RBC) and platelets in blood sampling from the aorta and splenic vein were estimated by an automatic blood cell counter. 3. Bolus injections of prostacyclin (1-100 ng/kg) into the splenic artery produced dose-dependent increases in splenic arterial blood flow and splenic diameter associated with significant decreases in splenic venous concentrations of WBC, RBC and platelets. When splenic blood flow was kept constant, similar changes in splenic diameter and blood cell counts were observed with prostacyclin injection. 4. Splenic dilation and haematological changes induced by prostacyclin were relatively more potent than those induced by prostaglandin E(2), acetylcholine, nitroglycerin or isoproterenol when doses producing a comparable increase in splenic blood flow were compared. 5. Infusion of prostacyclin (100 ng/kg per min) into the splenic artery caused a marked increase in splenic diameter, with immediate reductions in splenic venous concentrations of WBC, RBC and platelets, followed by significant reductions in these cell counts in the general circulation. 6. These results indicate that prostacyclin produces potent and flow-independent splenic dilation that may contribute to a decrease in circulating blood cell concentrations.

Comparative hemodynamic effects of nicorandil (NCR), nitroglycerin (NTG) and cromakalim (CRM) were examined in a canine model of acute congestive heart failure (CHF). CHF was produced by injections of saponin into coronary arteries of anesthetized dogs followed by volume loading and continuous i.v. infusion of methoxamine. After the treatment, aortic blood flow (AoF), left ventricular dP/dt and myocardial segment shortening (SS) markedly decreased, while the left ventricular end-diastolic pressure (LVEDP), the right atrial pressure (RAP) and the systemic vascular resistance (SVR) increased. NCR (n = 6), NTG (n = 6) and CRM (n = 8), which were administered i.v. after production of CHF, caused a comparable reduction in LVEDP. NCR and CRM profoundly increased AoF and SS but NTG did only slightly. On the other hand, NTG and NCR but not CRM significantly reduced RAP. Intracoronary NCR (n = 8) exerted no or similar effects on SS as well as systemic hemodynamic indices to those observed with i.v. NCR despite distinct coronary vasodilation. These results indicate that NCR may exert beneficial hemodynamic effects in an experimental CHF mainly due to lessening both afterload and preload rather than the coronary vasodilating effect.