There is extensive evidence that activation of the immune system is both necessary and required for the development of angiotensin II (Ang II)-induced hypertension in males. The purpose of this study was to determine whether sex differences exist in the ability of the adaptive immune system to induce Ang II-dependent hypertension and whether central and renal T-cell infiltration during Ang II-induced hypertension is sex dependent. Recombinant activating gene-1 (Rag-1)(-/-) mice, lacking both T and B cells, were used. Male and female Rag-1(-/-) mice received adoptive transfer of male CD3(+) T cells 3 weeks before 14-day Ang II infusion (490 ng/kg per minute). Blood pressure was monitored via tail cuff. In the absence of T cells, systolic blood pressure responses to Ang II were similar between sexes (Δ22.1 mm Hg males versus Δ18 mm : Hg females). After adoptive transfer of male T cells, Ang II significantly increased systolic blood pressure in males (Δ37.7 mm : Hg; P
Synaptic transmission between baroreceptor afferents and the nucleus tractus solitarius (NTS) is known to exhibit frequency-dependent depression. Reductions in neurotransmitter release and alterations in mechanisms regulating synaptic transmission are hypothesized to be involved in the activity-dependent depression observed in baroreceptor afferent neurons. The present study utilized cultured aortic baroreceptor neurons and the fluorescent dyes FM1-43 and FM2-10 to characterize the process of endocytosis or vesicle retrieval and its dependence on 1) frequency of neuronal activation, 2) metabotropic glutamate receptor (mGluR) activation, and 3) calcium concentrations inside and outside the cell. Endocytosis per spike, measured in fluorescence units after a 10-s stimulus applied at frequencies of 0.5 (53 +/- 4), 1.0 (23 +/- 1), and 10.0 Hz (2.7 +/- 0.2), was significantly depressed at higher frequencies. Blockade of group III mGluRs with (RS)-cyclopropyl-4-phosphonophenylglycine (CPPG) facilitated endocytosis at all frequencies, suggesting that this receptor subtype may be involved in the inhibition of endocytosis. Manipulating the extracellular and intracellular calcium concentrations subsequent to exocytosis had no effect on endocytosis. These results suggest that frequency-dependent depression of endocytosis observed in vitro could contribute to the frequency-dependent depression of baroreceptor afferent neurotransmission and that group III mGluRs inhibit endocytosis.
Activation of the area postrema by either electrical stimulation or chemical application of L-glutamate has been shown to result in an enhancement of cardiovascular baroreflexes similar to that seen with systemic infusions of arginine vasopressin (AVP). In addition, it has been found that the effects of AVP on baroreflex inhibition of renal sympathetic nerve activity (RSNA) are similar to those observed with phenylephrine following lesions of the area postrema or after partial denervation of baroreceptor afferents. The present study was undertaken to determine the role of baroreceptor afferent input on area postrema stimulation-induced decreases in sympathetic activity. In anesthetized rabbits, the responses of arterial pressure, heart rate, and RSNA to area postrema electrical stimulation were obtained before and after progressive sinoaortic denervation and vagotomy. Stimulation of the area postrema in carotid sinus-denervated animals consistently decreased RSNA in a frequency-dependent manner. However, following bilateral removal of both the aortic nerves and the vagi, electrical stimulation of the area postrema had no effect on RSNA. These results suggest that the ability of area postrema stimulation to inhibit RSNA is dependent on the presence of baroreceptor afferent input.
1. In addition to its effects at the renal tubules to influence water retention and at vascular smooth muscle to cause vasoconstriction, the hormone arginine vasopressin also appears to modulate cardiovascular reflex control of the sympathetic nervous system. Infusion or endogenous release of vasopressin results in enhanced baroreflex sympatho-inhibitory responses compared with other pressor agents. In addition, when changes in arterial pressure are imposed on an elevated background level of circulating vasopressin, due either to infusion or endogenous release, the arterial baroreflex response is shifted to lower pressures, and the maximum sympatho-excitation to a decrease in pressure is reduced. 2. Evidence suggests that vasopressin may influence cardiovascular reflex function at multiple sites. Nevertheless, the primary site involved in the effects of circulating vasopressin on baroreflex function appears to be in the central nervous system, specifically in the area postrema. Lesion of the area postrema abolishes the ability of circulating vasopressin to modulate arterial baroreflex and cardiopulmonary reflex function and electrical or chemical stimulation of this circumventricular organ mimics the effects of vasopressin. In addition, vasopressin has been shown to influence the activity of area postrema neurons in vivo and in vitro. Although not all studies agree, the effects of the area postrema and vasopressin on cardiovascular reflex function appear to be dependent on afferent input from peripheral baroreceptors. 3. Most evidence suggests that vasopressin exerts its effects on baroreflex function through a V1 vasopressin receptor mechanism. Systemic administration or microinjection into the area postrema of a specific V1 receptor antagonist abolishes the action of arginine vasopressin on arterial baroreflex and cardiopulmonary reflex control of the sympathetic nervous system. 4. The ability of vasopressin and the area postrema to influence baroreflex function appears to be dependent on an alpha 2-adrenoceptor mechanism at the level of the nucleus tractus solitarius (NTS). Blockade of alpha 2-adrenoceptors in the NTS abolishes the effects of vasopressin and the area postrema on the sympathetic nervous system. Facilitation of NTS processing of baroreceptor afferent inputs by the area postrema could contribute to the enhanced sympatho-inhibition and shift of the baroreflex curve to lower pressures during elevations in circulating vasopressin.