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J H Botting

Publications and source records attributed to J H Botting.

At least 19 recordsLinked to original sources
PubMed1991

Adrenaline inhibits adenosine diphosphate induced intravascular aggregation of rat platelets through stimulation of alpha 2 adrenoceptors.

STUDY OBJECTIVE: The aim was to determine the receptors involved in the antiaggregatory effects of adrenaline in the rat. DESIGN: The 111indium oxine technique was used to evaluate ADP induced pulmonary accumulation of 111In labelled platelets in adrenalectomised rats (ie, no endogenous adrenaline) in the absence of anticoagulants. Adrenaline was infused (10, 20 and 40 micrograms.kg-1.h-1) and ADP aggregation measured. Adrenoceptor agonists, isoprenaline, methoxamine, and BHT 933, were given to evaluate whether they mimic the adrenaline effects. Adrenoceptor antagonists, yohimbine, propranolol, prazosin, and WY 26392, were given to assess whether they block the adrenaline effects. MEASUREMENTS AND MAIN RESULTS: In all cases, pulmonary accumulation of platelets was measured in response to ADP. Adrenaline dose dependently inhibited platelet aggregation. BHT 933 (1.5 micrograms.kg-1.min-1) mimicked, while phentolamine (1 mg.kg-1), yohimbine (2.5 mg.kg-1), and WY 26392 (0.1, 1.0, 5.0 mg.kg-1) blocked, the adrenaline effects. Methoxamine (3.3 micrograms.kg-1.min-1) produced a relatively weak non-specific inhibition of ADP aggregation. Isoprenaline (33 ng.kg-1.min-1) did not mimic the effects of adrenaline, neither did propranolol (1 mg.kg-1) affect the adrenaline inhibition of the aggregatory responses to ADP. Indomethacin (3 mg.kg-1) blocked the inhibitory effects of adrenaline. CONCLUSIONS: Adrenaline stimulates alpha receptors on platelets but inhibits platelet aggregation. There is no evidence to suggest that beta receptors participated in the effects produced by adrenaline. There is a role for cyclo-oxygenase products in the inhibitory effects of adrenaline on aggregation.

Adenosine Diphosphate↗
PubMed1990

Indium-111 oxine technique of studying platelet aggregation in vivo. Some physiological considerations.

Intravascular aggregation in response to ADP, thrombin, arachidonate and collagen has been studied in the rat with a view to throwing more light on the validity, the reproducibility and physiology of the model. The radioisotopic technique of labelling platelets with indium-111 oxine was employed. The model is minimally invasive and involves collecting blood from donor rats, separating and labelling their platelets with indium-111 oxine and assessing the accumulation of platelets in the lungs of recipient rats following the intravascular administration of aggregating agents. Of the parameters evaluated, percentage peak increase in radio-labelled platelet count and area under the curve are good parameters of expressing aggregatory responses. Of the visceral organs evaluated, the lung is the most important organ for assessing platelet accumulation. Of the vascular routes examined, no aggregatory response occurred in the lungs when ADP was injected via any of the intra-arterial routes, and of the intravenous routes, injection via the tail vein gave the highest response. The results of this investigation provide some more detailed technical information to take note of when studying platelet aggregation in vivo by this model. The results also highlight the physiological phenomenon involved.

Adenosine Diphosphate↗
PubMed1988

The influence of adrenaline on gender difference in adenosine diphosphate-induced aggregation of platelets in the rat.

The role of adrenaline on the inhibitory effects of physiological levels of oestradiol on ADP-induced intravascular aggregation has been studied. Platelets from pro-oestrous female rats aggregated less than those from dioestrous and male rats. Following adrenalectomy, there was no longer any difference(s) in the aggregability of the platelets to ADP in any of the rats. Adrenaline infusion (20 mg kg-1 hr-1) restored platelet aggregation to preadrenalectomy levels in pro-oestrous rate. Measurement of spontaneous fibrinolytic activity of the plasma showed highest value in pro-oestrous rats. Adrenalectomy reduced, while adrenaline infusion increased the fibrinolytic activity. The results suggest that the inhibitory effects of oestradiol on intravascular aggregation are dependent on endogenous adrenaline possibly working through the fibrinolytic pathway.

Adenosine Diphosphate↗
PubMed1988

Cryptolepine inhibits platelet aggregation in vitro and in vivo and stimulates fibrinolysis ex vivo.

1. Cryptolepine--the methylquindolanol alkaloid of Cryptolepsis sanguinolenta was evaluated for its antiplatelet and fibrinolytic effects. 2. It exhibited antiplatelet effects in vitro in human, rabbit and rat PRP with EC50 values ranging between 8.1 x 10(-8) M and 1.7 x 10(-7) M for ADP, AA and thrombin. 3. In the rat, it inhibited ADP-aggregation in vivo with delayed onset and prolonged action. 4. In vitro, cryptolepine disaggregated (dose-dependently) platelets aggregated by ADP, AA and thrombin. 5. In addition, it exhibited an indirect fibrinolytic action in the rat possibly by causing the release of plasminogen activators from the vascular endothelium.

Adenosine Diphosphate↗
PubMed1987

Inhibition of adenosine diphosphate-induced intravascular aggregation of rat platelets in vivo by 6-oxo-prostaglandin E1.

The antiaggregatory effects of 6-oxo-PGE1 were evaluated in vivo in the rat using a minimally invasive technique involving 111-Indium labelling of platelets. The antiaggregatory effects on adenosine diphosphate-induced aggregation were compared with those of prostacyclin (PGI2) and prostaglandin E1 (PGE1) following slow infusions and bolus injections. The rank order of antiaggregatory potency was PGI2 greater than 6-oxo-PGE1 greater than PGE1 while the rank order of duration of antiaggregatory effects was PGE1 greater than 6-oxo-PGE1 greater than PGI2. The kinetics of the antiaggregatory effects of these prostaglandins suggests that such actions are not mediated by direct effects on platelets, but through a secondary mechanism.

Adenosine Diphosphate↗
PubMed1986

A minimally invasive technique for the study of intravascular platelet aggregation in anesthetized rats.

A method for monitoring platelet aggregation in vivo in the rat is described, using platelets labeled with indium3+ oxine and recording the increase in radioactivity count in the lung after injection of adenosine diphosphate and collagen. The effects of adenosine diphosphate and collagen are reproducible between animals. 5-Hydroxytryptamine creatine sulfate, which is inactive on rat platelets in vitro, causes aggregation in vivo, and adrenaline, which is proaggregatory in vitro inhibits adenosine diphosphate-induced aggregation in vivo. Female rats are relatively insensitive to the aggregating agents, particularly during proestrus, although when platelets from proestrus females were injected into male rats, their sensitivity was increased. Platelets from male rats injected into female rats in proestrus have low sensitivity.

Adenosine Diphosphate↗
PubMed1984

Neuropeptide-induced contraction and relaxation of the mouse anococcygeus muscle.

Isometric tension responses to neuropeptides were recorded from anococcygeus muscles isolated from male mice. This smooth muscle tissue is innervated by inhibitory nonadrenergic, noncholinergic nerves that resemble, ultrastructurally, the peptidergic neurons of the gastrointestinal tract; the physiological function of the anococcygeus is not known. Slow sustained contractions were produced by oxytocin (0.2-20 nM), [Arg8]vasopressin (0.4-200 nM), and [Arg]-vasotocin (0.4-100 nM); the mouse anococcygeus is, therefore, one of the few examples of nonvascular smooth muscle from male mammals to respond to low concentrations of oxytocin and related peptides. Substance P (0.5-8 microM) caused distinctive, biphasic increases in muscle tone of some, but not all, preparations. Other neuropeptides producing contractions were neurotensin (2-100 microM) and thyrotropin-releasing hormone (2-100 microM); the responses were of similar time course and displayed selective cross-desensitization, suggesting that these two peptides act through a common distinct mechanism. Tetradecapeptide somatostatin (10-80 microM) and its analog urotensin II (0.1-5 microM), a dodecapeptide from the urophysis of the teleost fish Gillichthys mirabilis, produced similar slowly developing relaxations of carbachol-induced tone. Piscine urotensin II, of which there are no reported effects on nonvascular mammalian systems, was 20-50 times more potent than somatostatin, a well-established mammalian hormone. Of the peptides studied, only vasoactive intestinal polypeptide (0.05-1 microM) caused rapid powerful relaxations in low concentrations; this is consistent with its proposed involvement in nonadrenergic, noncholinergic neurotransmission in the mouse anococcygeus.

Animals↗
PubMed1983

The effect of modification of sympathetic activity on responses to ligation of a coronary artery in the conscious rat.

1 Ligation of a coronary artery was performed in conscious rats whose sympathetic system activity had been altered by various treatments. 2 beta-Adrenoceptor blockade with acute (0.2 mg kg-1 plus 0.1 micrograms kg-1 min-1) or chronic (50-60 mg kg-1 daily for 12 days) propranolol treatment had little effect on arrhythmias, or other responses to ligation. 3 Abrupt withdrawal of chronic propranolol two days before ligation was also without effect. 4 Reduction of sympathetic activity acutely with labetalol (5 mg kg-1), or chronically with adrenomedullectomy and 6-hydroxydopamine treatment, accentuated the adverse effects of ligation. 5 The results of this study suggest that, while activity of the sympathetic system is not detrimental during ligation in the conscious rat, it may be important for survival.

Adrenalectomy↗
PubMed1981

The influence of sex hormones on rat platelet sensitivity to adenosine-diphosphate.

The sensitivity of rat platelets to the aggregating agent adenosine-diphosphate (ADP) was studied. Platelets form male and female rats demonstrated comparable sensitivity. Neither ovariectomy nor castration altered platelet sensitivity to ADP. However platelets form mock-operated female, but not mock-operated male rats were less sensitive. Administration of physiological doses of 17 beta-oestradiol to ovariectomised rats reduced platelet sensitivity. Administration of 17 beta-oestradiol to mock operated female rats increased platelet sensitivity to ADP. The results suggest that physiological amounts of oestrogen induce a loss of platelet sensitivity following surgery or stress, whereas higher concentrations of oestrogens increase platelet sensitivity.

Adenosine Diphosphate↗
PubMed1981

Spurious effects of commercial preparations of oxytocin on the isolated vas deferens of the rat.

1 The inhibitory effect of a commercial preparation of oxytocin (Syntocinon) was studied on the isolated vas deferens of the rat. 2 The inhibition of contractions to agonists and to field stimulation obtained were mimicked by appropriate dilutions of chlorbutol, a preservative present in Syntocinon. 3 Preservative-free synthetic oxytocin had no inhibitory effect on the tissue and slightly potentiated contractions evoked by field stimulation. 4 It is concluded that inhibitory effects of Syntocinon on the vas deferens are due to chlorbutol, not oxytocin.

Animals↗