Mechanisms involved in the cardiovascular effects caused by acute osmotic stimulation in conscious rats.

Both the autonomic nervous system and the neuroendocrine system are activated by osmotic stimulation (OS) evoking cardiovascular effects. The current study investigated the mechanisms involved in the cardiovascular responses evoked by an acute osmotic stimulus with intraperitoneal (i.p.) injection of either isotonic (0.15 M NaCl) or hypertonic saline (0.6 M NaCl) in conscious rats. Hypertonic saline increased mean arterial pressure (MAP) and heart rate (HR) for 30 min, as well as plasma osmolality and sodium content. Urinary sodium and urinary volume were also increased. Pretreatment with the ganglion blocker pentolinium (i.v.) did not affect the pressor response, but significantly decreased the tachycardic response caused by OS. Pretreatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (i.v.) reduced the pressor response, without affecting the tachycardic response evoked by the hypertonic OS. Neither the pressor nor the tachycardic response to OS was affected by pretreatment with either the oxytocin receptor antagonist atosiban or the α1-antagonist prazosin. Pretreatment with the ß1-antagonist atenolol had no effect on the pressor response, but markedly decreased the tachycardic response evoked by OS. Results indicate that i.p. hypertonic OS-evoked pressor response is mediated by the release of vasopressin, with a minor influence of the vascular sympathetic input.LAY SUMMARYIncreased plasma osmolality, such as that observed during dehydration or salt intake, is a potent stimulus yielding to marked cardiovascular and neuroendocrine responses. The intraperitoneal (i.p.) injection of hypertonic saline solution is a commonly used animal model to cause a sustained increase in plasma osmolality, leading to a cardiovascular response characterized by sustained blood pressure and heart increases, whose systemic mechanisms were presently studied. Our findings indicate that the pressor response to the i.p. osmotic stimulus (OS) is mediated mainly by the release of vasopressin into the blood circulation with a minor or even the noninvolvement of the vascular sympathetic nervous system, whereas activation of the sympathetic-cardiac system mediates the tachycardic response to OS.

The Supraoptic Nucleus of the Hypothalamus Modulates Autonomic, Neuroendocrine, and Behavioral Responses to Acute Restraint Stress in Rats.

AIMS: Acute restraint stress (RS) has been reported to cause neuronal activation in the supraoptic nucleus of the hypothalamus (SON). The aim of the study was to evaluate the role of SON on autonomic (mean arterial pressure [MAP], heart rate [HR], and tail temperature), neuroendocrine (corticosterone, oxytocin, and vasopressin plasma levels), and behavioral responses to RS. METHODS: Guide cannulas were implanted bilaterally in the SON of male Wistar rats for microinjection of the unspecific synaptic blocker cobalt chloride (CoCl2, 1 mM) or vehicle (artificial cerebrospinal fluid, 100 nL). A catheter was introduced into the femoral artery for MAP and HR recording. Rats were subjected to RS, and it was studied the effect of microinjection of CoCl2 or vehicle into the SON on pressor and tachycardic responses, drop in tail temperature, plasma oxytocin, vasopressin, and corticosterone levels, and anxiogenic-like effect induced by RS. RESULTS: SON pretreatment with CoCl2 reduced the RS-induced MAP and HR increase, without affecting the RS-evoked tail temperature decrease. Microinjection of CoCl2 into areas surrounding the SON did not affect RS-induced increase in MAP and HR, reinforcing the idea that SON influences RS-evoked cardiovascular responses. Also, SON pretreatment with CoCl2 reduced RS-induced increase in corticosterone and oxytocin, without affecting vasopressin plasma levels, suggesting its involvement in RS-induced neuroendocrine responses. Finally, the CoCl2 microinjection into SON inhibited the RS-caused delayed anxiogenic-like effect. CONCLUSION: The results indicate that SON is an important component of the neural pathway that controls autonomic, neuroendocrine, and behavioral responses induced by RS.

Role of the autonomic nervous system and baroreflex in stress-evoked cardiovascular responses in rats.

Restraint stress (RS) is an experimental model to study stress-related cardiovascular responses, characterized by sustained pressor and tachycardiac responses. We used pharmacologic and surgical procedures to investigate the role played by sympathetic nervous system (SNS) and parasympathetic nervous system (PSNS) in the mediation of stress-evoked cardiovascular responses. Ganglionic blockade with pentolinium significantly reduced RS-evoked pressor and tachycardiac responses. Intravenous treatment with homatropine methyl bromide did not affect the pressor response but increased tachycardia. Pretreatment with prazosin reduced the pressor and increased the tachycardiac response. Pretreatment with atenolol did not affect the pressor response but reduced tachycardia. The combined treatment with atenolol and prazosin reduced both pressor and tachycardiac responses. Adrenal demedullation reduced the pressor response without affecting tachycardia. Sinoaortic denervation increased pressor and tachycardiac responses. The results indicate that: (1) the RS-evoked cardiovascular response is mediated by the autonomic nervous system without an important involvement of humoral factors; (2) hypertension results primarily from sympathovascular and sympathoadrenal activation, without a significant involvement of the cardiac sympathetic component (CSNS); (3) the abrupt initial peak in the hypertensive response to restraint is sympathovascular-mediated, whereas the less intense but sustained hypertensive response observed throughout the remaining restraint session is mainly mediated by sympathoadrenal activation and epinephrine release; (4) tachycardia results from CSNS activation, and not from PSNS inhibition; (5) RS evokes simultaneous CSNS and PSNS activation, and heart rate changes are a vector of both influences; (6) the baroreflex is functional during restraint, and modulates both the vascular and cardiac responses to restraint.

α1 and α2-adrenoceptors in the medial amygdaloid nucleus modulate differently the cardiovascular responses to restraint stress in rats.

Medial amygdaloid nucleus (MeA) neurotransmission has an inhibitory influence on cardiovascular responses in rats submitted to restraint, which are characterized by both elevated blood pressure (BP) and intense heart rate (HR) increase. In the present study, we investigated the involvement of MeA adrenoceptors in the modulation of cardiovascular responses that are observed during an acute restraint. Male Wistar rats received bilateral microinjections of the selective α1-adrenoceptor antagonist WB4101 (10, 15, and 20 nmol/100 nL) or the selective α2-adrenoceptor antagonist RX821002 (10, 15, and 20 nmol/nL) into the MeA, before the exposure to acute restraint. The injection of WB4101 reduced the restraint-evoked tachycardia. In contrast, the injection of RX821002 increased the tachycardia. Both drugs had no influence on BP increases observed during the acute restraint. Our findings indicate that α1 and α2-adrenoceptors in the MeA play different roles in the modulation of the HR increase evoked by restraint stress in rats. Results suggest that α1-adrenoceptors and α2-adrenoceptors mediate the MeA-related facilitatory and inhibitory influences on restraint-related HR responses, respectively.

Cardiovascular responses to microinjection of noradrenaline into the medial amygdaloid nucleus of conscious rats result from α2-receptor activation and vasopressin release.

The medial amygdaloid nucleus (MeA) is involved in the modulation of physiological and behavioral processes, as well as regulation of the autonomic nervous system. Moreover, MeA electrical stimulation evokes cardiovascular responses. Thus, as noradrenergic receptors are present in this structure, the present study tested the effects of local noradrenaline (NA) microinjection into the MeA on cardiovascular responses in conscious rats. Moreover, we describe the types of adrenoceptor involved and the peripheral mechanisms involved in the cardiovascular responses. Increasing doses of NA (3, 9, 27 or 45 nmol/100 nL) microinjected into the MeA of conscious rats caused dose-related pressor and bradycardic responses. The NA cardiovascular effects were abolished by local pretreatment of the MeA with 10 nmol/100 nL of the specific α2-receptor antagonist RX821002, but were not affected by local pretreatment with 10 nmol/100 nL of the specific α1-receptor antagonist WB4101. The magnitude of pressor response evoked by NA microinjected into the MeA was potentiated by intravenous pretreatment with the ganglion blocker pentolinium (5 mg/kg), and blocked by intravenous pretreatment with the selective V1-vasopressin antagonist dTyr(CH2)5 (Me)AVP (50 µg/kg). In conclusion, our results show that microinjection of NA into the MeA of conscious rats activates local α2-adrenoceptors, evoking pressor and bradycardic responses, which are mediated by vasopressin release.

A functional selective effect of oxytocin secreted under restraint stress in rats.

Restraint stress (RS) is an unavoidable stress model that triggers activation of the autonomic nervous system, endocrine activity, and behavioral changes in rodents. Furthermore, RS induces secretion of oxytocin into the bloodstream, indicating a possible physiological role in the stress response in this model. The presence of oxytocin receptors in vessels and heart favors this possible idea. However, the role of oxytocin secreted in RS and effects on the cardiovascular system are still unclear. The aim of this study was to analyze the influence of oxytocin on cardiovascular effects during RS sessions. Rats were subjected to pharmacological (blockade of either oxytocin, vasopressin, or muscarinic receptors) or surgical (hypophysectomy or sinoaortic denervation) approaches to study the functional role of oxytocin and its receptor during RS. Plasma levels of oxytocin and vasopressin were measured after RS. RS increased arterial pressure, heart rate, and plasma oxytocin content, but not vasopressin. Treatment with atosiban (a Gi biased agonist) inhibited restraint-evoked tachycardia without affecting blood pressure. However, this effect was no longer observed after sinoaortic denervation, homatropine (M2 muscarinic antagonist) treatment or hypophysectomy, indicating that parasympathetic activation mediated by oxytocin secreted to the periphery is responsible for blocking the increase in tachycardic responses observed in the atosiban-treated group. Corroborating this, L-368,899 (oxytocin antagonist) treatment showed an opposite effect to atosiban, increasing tachycardic responses to restraint. Thus, this provides evidence that oxytocin secreted to the periphery attenuates tachycardic responses evoked by restraint via increased parasympathetic activity, promoting cardioprotection by reducing the stress-evoked heart rate increase.

The medial amygdaloid nucleus modulates the baroreflex activity in conscious rats.

The medial amygdaloid nucleus (MeA) is involved in cardiovascular control. In the present study we report the effect of MeA pharmacological ablations caused by bilateral microinjections of the nonselective synaptic blocker CoCl2 on cardiac baroreflex responses in rats. MeA synaptic inhibition evoked by local bilateral microinjection of 100 nL of CoCl2 (1 mM) did not affect blood pressure or heart rate baseline, suggesting no tonic MeA influence on resting cardiovascular parameters. However, 10 min after CoCl2 microinjection into the MeA of male Wistar rats, the reflex bradycardic response evoked by intravenous infusion of phenylephrine was significantly enhanced when compared with the reflex bradycardic response observed before CoCl2. The treatment did not affect the tachycardic responses to the intravenous infusion of sodium nitroprusside (SNP). Baroreflex activity returned to control values 60 min after CoCl2 microinjections, confirming a reversible blockade. The present results indicate an involvement of the MeA in baroreflex modulation, suggesting that synapses in the MeA have an inhibitory influence on the bradycardic component of the baroreflex in conscious rats.