Cardiovascular Effects Of Noradrenaline Research Articles

Mechanisms involved in the pressor response to noradrenaline microinjection into the supraoptic nucleus of unanesthetized rats

We report on the cardiovascular effects of noradrenaline (NA) microinjection into the hypothalamic supraoptic nucleus (SON) as well as the central and peripheral mechanisms involved in their mediation. Microinjections of NA 1, 3, 10, 30 or 45 nmol/100 nL into the SON caused dose-related pressor and bradycardiac response in unanesthetized rats. The response to NA 10 nmol was blocked by SON pretreatment with 15 nmol of the alpha(2)-adrenoceptor antagonist RX821002 and not affected by pretreatment with equimolar dose of the selective alpha(1)-adrenoceptor antagonist WB4101, suggesting that local alpha(2)-adrenoceptors mediate these responses. Pretreatment of the SON with the nonselective beta-adrenoceptor antagonist propranolol 15 nmol did not affect the pressor response to NA microinjection of into the SON. Moreover, the microinjection of the 100 nmol of the selective alpha(1)-adrenoceptor agonist methoxamine (MET) into the SON did not cause cardiovascular response while the microinjection of the selective alpha(2)-adrenoceptor agonists BHT920 (BHT, 100 nmol) or clonidine (CLO, 5 nmol) caused pressor and bradycardiac responses, similar to that observed after the microinjection of NA. The pressor response to NA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium and was blocked by intravenous pretreatment with the V(1)-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP, suggesting an involvement of circulating vasopressin in this response. In conclusion, our results suggest that pressor responses caused by microinjections of NA into the SON involve activation of local alpha(2)-adrenoceptor receptors and are mediated by vasopressin release into circulation.

Pressor effects of noradrenaline injected into the lateral septal area of unanesthetized rats

The lateral septal area (LSA) is involved in central cardiovascular control. In the present study, we report on the cardiovascular effects of noradrenaline (NA) injection into the LSA of unanesthetized rats, as well as on local receptors and peripheral mechanisms involved in their mediation. Microinjections of NA (9, 15, 21, 27 or 45 nmol) caused long-lasting, dose-related pressor and bradycardic responses in unanesthetized rats. No responses were observed when the dose of 21 nmol of NA was microinjected into medial septal area or lateral ventricle suggesting a main action at the LSA. No changes were observed in arterial pressure and heart rate when NA was injected in the LSA of anesthetized rats. The effects of 21 nmol of NA were abolished by local pretreatment with 10 nmol of the specific α 1-receptor antagonist WB 4101, but were not affected by pretreatment with 10 nmol of the specific α 2-receptor antagonist RX 821002. The magnitude of pressor response to NA in the LSA was increased by i.v. pretreatment with the ganglion blocker pentolinium (10 mg/kg) and significantly reduced by i.v. pretreatment with the V 1-vasopressin receptor antagonist dTyr (CH2)5(Me) AVP (50 μg/kg). No pressor response to NA was observed in hypophysectomized rats. The present observation of α 1-adrenoceptor-mediated pressor responses after local injection of NA confirms earlier evidence of a LSA involvement in central cardiovascular control. Pretreatment with the α 1-adrenoceptor antagonist WB-4101 did not affect baseline blood pressure or heart rate suggesting no tonic involvement of septal adrenergic mechanisms suggesting a modulatory LSA influence on cardiovascular control. Additionally, the blockade of the pressor response by the i.v. pretreatment with a V 1-vasopressin antagonist indicates that noradrenergic LSA mechanisms modulate vasopressin release.

The ruthenium-based nitric oxide scavenger, AMD6221, augments cardiovascular responsiveness to noradrenaline in rats with streptozotocin-induced diabetes

Excess production of nitric oxide by inducible nitric oxide synthase (iNOS) has been implicated in cardiovascular dysfunction associated with the acute phase of diabetes mellitus. We examined if the selective nitric oxide scavenger, AMD6221 (ruthenium[hydrogen(diethylenetrinitrilo)pentaacetato] chloride) improved cardiovascular function in rats with streptozotocin (60 mg/kg, i.v.)-induced diabetes. The cardiovascular effects of noradrenaline (16.5 nmol/kg/min, i.v.) were measured in thiobutabarbitone-anaesthetised diabetic and control rats before and after acute administration of AMD6221 (80 mg/kg). Rats in the acute phase of diabetes (3 weeks post injection of streptozotocin) had impaired mean arterial pressure, left ventricular systolic pressure and maximum rate of increase (+ d P/d t) and decrease (− d P/d t) of left ventricular pressure responses to noradrenaline compared with control rats. AMD6221 significantly augmented noradrenaline-induced increases in left ventricular systolic pressure and ± d P/d t in the diabetic but not control rats. The results show that selective scavenging of nitric oxide by AMD6221 improved cardiac response to noradrenaline in rats with streptozotocin-induced diabetes.

Cardiovascular effects of noradrenaline in hypovolemic haemorrhage: role of inducible nitric oxide synthase

Hypovolemia has been associated with the induction of nitric oxide synthase which is believed to result in an over-production of nitric oxide. In the present study, we have examined the effects of noradrenaline following haemorrhage on cardiac output, blood pressure, mean circulatory filling pressure and vascular resistance in anaesthetized rats after pre-treatment with nitric oxide synthase inhibitor, l- N 6-(1-iminoethyl)lysine or dexamethasone. Hypovolemic haemorrhage resulted in induction of nitric oxide synthase, as measured in lungs, and both dexamethasone and l- N 6-(1-iminoethyl)lysine inhibited the activity of the inducible form of nitric oxide synthase. An infusion of noradrenaline significantly increased cardiac output, blood pressure and mean circulatory filling pressure in animals pre-treated with l- N 6-(1-iminoethyl)lysine and dexamethasone when compared with saline pre-treatment. In addition, the administration of noradrenaline significantly reduced venous resistance in animals pre-treated with l- N 6-(1-iminoethyl)lysine when compared with saline pre-treatment. The results of this investigation indicated that the impact of noradrenaline on cardiac output, blood pressure and mean circulatory filling pressure was greater in hypovolemic rats treated with l- N 6-(1-iminoethyl)lysine or dexamethasone. In addition, we found that in the hypovolemic state, the greater increase in cardiac output during the infusion of noradrenaline after inhibition of nitric oxide synthase was predominantly due to reduced resistance to venous return.

A Study of Some Cardiovascular Effects of Noradrenaline in Pregnant and Non-Pregnant Women

A Study of Some Cardiovascular Effects of Noradrenaline in Pregnant and Non-Pregnant Women

Somatostatin: Interaction with the sympathetic nervous system in guinea pigs

We have investigated the cardiovascular effects of somatostatin (SS) in anesthetized guinea pigs. SS was found to produce a dose-dependent vasodepressor effect and bradycardia. The size of the vasodepressor response to SS was dependent on the pre-injection level of blood pressure. The higher the blood pressure was, the larger was the response to SS. Atropine (1 mg kg −1) did not alter the effects of SS thus suggesting that SS neither activates cholinergic nerves nor interacts with muscarinic receptors. SS (5 μg kg −1 min −1) markedly inhibited the pressor effects of dimethylphenylpiperazinium (DMPP), a relatively specific ganglionic stimulant, and of isoproterenol, a beta receptor agonist, without interfering with their positive chronotropic effects. The pressor effects and tachycardia evoked by bolus injections of noradrenaline and of tyramine were usually enhanced during SS infusions. Guanethidine, a drug known to paralyse adrenergic neurons, modified similarly to SS, the cardiovascular effects of noradrenaline and of DMPP. The results suggest that the vasodepressor effect of SS results from a selective depression of the sympathetic outflow to the blood vessels via a presynaptic inhibitory effect on adrenergic neurons. The slowing of heart rate caused by SS is most likely the result of a direct depressant effect on the sinoatrial node.

Reduction of cardiovascular responses to some sympathomimetic amines during hypercapnia

The cardiovascular effects of noradrenaline, adrenaline, isoprenaline and orciprenaline were examined in rats before, during and after a period of hypercapnia produced by ventilation with 10% CO 2 in air. This procedure increased the PCO 2 from 37 to 79 mm Hg and was accompanied by an acidosis with a fall in pH from 7.39 to 7.08. The increases in heart rate in response to adrenaline, isoprenaline and orciprenaline were abolished or reduced during hypercapnia. The pressor responses to noradrenaline and adrenaline, and the depressor responses to isoprenaline and orciprenaline were also reduced. The changes in responses to these amines produced by hypercapnia were rapid in onset, and were restored towards control levels when the animals were returned to ventillation with air. These effects were not due to desensitization of receptors by catecholamines released from the adrenals, since in adrenalectomized rats hypercapnia produced the same changes in responses to noradrenaline and isoprenaline as in intact rats. They may have been due to desensitization of receptors by catecholamines released from sympathetic nerves, by the depressant effect of a high level of CO 2, or to changes in receptor configuration with the fall in pH. The findings do not suggest any increased hazard of sympathomimetic bronchodilators in severe asthma with hypercapnia.

Potentiating action of desmethylimipramine on the cardiovascular effects of noradrenaline and some other pressor agents.

AbstractThe influence of desmethylimipramine (DMI) on the cardiovascular responses to i.v. injected noradrenaline (NA), adrenaline, metaraminol and isoprenaline, as well as to some chemically unrelated pressor agents (angiotensin, vasopressin, and the vasopressin analogue felypressin), was studied in anesthetized dogs and cats. The cardiovascular effects of NA were potentiated very markedly by moderate doses of DMI (0.1–1.0 mg/kg). The responses to adrenaline and metaraminol were only slightly potentiated. In the case of adrenaline, DMI was slightly more effective in enhancing the pressor action of this amine after partial β‐blockade (propranolol). In analogy with the carotid occlusion response, the effect on the peripheral vascular resistance elicited by electrical stimulation of the lumbar sympathetic nerves was not significantly potentiated by DMI.A method of “delayed autoperfusion” was developed to record reflex vasomotor counter‐regulation. DMI was found to reduce the activity of this counter‐regulation suggesting that this may be one way in which this drug potentiates the cardiovascular effects of the non‐catecholamine pressor agents.

Simultaneous sensitization to metabolic and cardiovascular effects of noradrenaline.

(1969). Simultaneous Sensitization to Metabolic and Cardiovascular Effects of Noradrenaline. Archives Internationales de Physiologie et de Biochimie: Vol. 77, No. 4, pp. 731-740.