Glutamatergic and GABAergic inputs to the RVL mediate cardiovascular adjustments to noxious stimulation.

Stimulation of cutaneous and muscle afferents induces several cardiovascular adjustments such as hypertension, tachycardia, and muscle vasodilation. Although previous studies have demonstrated that the rostral ventrolateral medulla (RVL) mediates sympathoexcitation and pressor responses to sciatic nerve stimulation (SNS), whether it also mediates blood flow adjustments remains unclear. Therefore, in the present study, we examined the role of the RVL in the vasodilation induced by SNS and the possible neurotransmitters involved. In Urethane-anesthetized, paralyzed, and artificially ventilated rats, SNS (square pulses, 1 ms, 20 Hz, 800--1200 microA, 10 s) produced increases in blood pressure, heart rate, blood flow, and vascular conductance of the stimulated limb. Unilateral microinjection of kainic acid (2 nmol/100 nl) into the RVL contralateral to the stimulated limb abolished cardiovascular adjustments to SNS. Unilateral microinjections of kynurenic acid (2 nmol/100 nl) selectively abolished the pressor response to SNS, whereas bicuculline (400 pmol/100 nl) abolished the increases in blood flow without changing the pressor response. These results suggest that glutamatergic synapses within the RVL mediate pressor responses, whereas GABAergic synapses may mediate the vasodilation to SNS.

NO-containing factors mediate hindlimb vasodilation produced by superior laryngeal nerve stimulation.

The electrical stimulation (ES) of the superior laryngeal nerve (SLN) produces reflex vasodilation in the rat hindlimb. This study determined whether this vasodilation is mediated by the release of nitric oxide (NO)-containing factors (NOF) from NO synthase (NOS)-positive postganglionic lumbar sympathetic fibers that innervate the rat hindlimb vasculature. ES of the SLN (1-10 Hz for 15 s) produced frequency-dependent reductions in mean arterial blood pressure (MAP) and hindlimb and mesenteric (MR) vascular resistances. The hindlimb vasodilation was not observed in rats in which the lumbar sympathetic trunk was transected 7-10 days previously. The falls in hindquarter vascular resistance (HQR) produced by lower intensity ES of the SLN were virtually abolished by the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI, 45 mg/kg i.v.). The fall in HQR produced by 10 Hz ES of the SLN was not affected by 7-NI. The falls in MR produced by 1-10 Hz ES of the SLN were unaffected by 7-NI. Four consecutive episodes of ES at 10 Hz produced pronounced and equivalent reductions in MAP, HQR, and MR. After administration of 7-NI, the first ES produced similar hemodynamic responses to those observed before injection. However, each subsequent ES produced progressively and markedly smaller falls in HQR, whereas each episode of ES produced similar falls in MR. These results suggest that the reflex vasodilation in the rat hindlimb produced by ES of the SLN involves the release of newly synthesized and performed stores of NOF from NOS-positive postganglionic lumbar sympathetic nerves.

Neurogenically derived nitrosyl factors mediate sympathetic vasodilation in the hindlimb of the rat.

Skeletal muscle vasculature of the hindlimb is innervated by a sympathetic noncholinergic vasodilator system. The aim of this study was to determine whether this vasodilator system may represent postganglionic lumbar sympathetic neurons that synthesize and release nitric oxide (NO) or related NO-containing factors. We examined whether NO synthase (NOS)-positive postganglionic lumbar nerves innervate the hindlimb vasculature of the rat and whether the hindlimb vasodilation produced by electrical stimulation of the lumbar sympathetic chain of anesthetized rats is reduced after the systemic administration of the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI). Subpopulations of lumbar sympathetic cell bodies stained intensely for NOS. Postganglionic fibers and varicosities within the iliac and femoral arteries also stained for NOS. Double ligation of the lumbar chain demonstrated that NOS was transported from the cell bodies toward the peripheral terminals. Low-intensity electrical stimulation of the lumbar chain produced a pronounced hindlimb vasodilation that was markedly diminished by pretreatment with 7-NI (45 mg/kg i.v.). In contrast, the vasodilator potency of acetylcholine and S-nitrosocysteine were augmented by 7-NI. These results suggest that postganglionic lumbar sympathetic neurons may synthesize and release NO-containing factors.

A fall in arterial blood pressure produced by inhibition of the caudalmost ventrolateral medulla: the caudal pressor area.

The caudal edge of the ventrolateral medulla was mapped to localize sites where microinjections of L-glutamate (L-glu) produce pressor responses in paralyzed and artificially ventilated urethane-anesthetized rats. Pressor responses ranging from 15 to 65 mmHg were obtained when L-Glu (0.25 M, 200 nl) was microinjected in the ventral medullary surface within an area localized between the rootlets of the XII and first cervical nerves, lateral to the pyramids and just medial to the spinal roots of the XI cranial nerve. This area has been called the caudal pressor area (CPA). Inhibition of the CPA by microinjection of GABA or glycine resulted in marked falls (15-45 mmHg) of arterial blood pressure (AP). Hypotension in response to CPA inhibition was also obtained in unanesthetized decerebrate animals. Cardiovascular responses to CPA stimulation or inhibition depend on the activity of neurons in the rostral ventrolateral medulla (RVLM). During hypotension provoked by RVLM inhibition, pressor responses to CPA stimulation were abolished. Conversely, pressor responses to RVLM stimulation were maintained during hypotension produced by inhibition of CPA. Pressor response to bilateral carotid occlusion were not reduced by CPA inhibition. We conclude that cells in the caudal most ventrolateral medulla exert a tonic pressor activity that contributes to maintenance of basal levels of the vasomotor tone and arterial blood pressure, its inhibition, however, does not prevent the pressor response to carotid occlusion.

Putative pathways involved in cardiovascular responses evoked from the caudal pressor area.

1. The caudal pressor area (CPA) is a recently identified site within the ventrolateral medulla which is involved in cardiovascular regulation. CPA chemical stimulation by L-glutamate produces an increase in arterial blood pressure (ABP) while its inhibition by GABA or glycine evokes marked hypotension. In the present study, we sought to determine the potential neural pathways underlying these responses. 2. In urethane-anesthetized, paralyzed, artificially ventilated rats, CPA inhibition by bilateral microinjection of the inhibitory amino acid glycine (Gly, 100 nmol 200 nl-1 site-1) produced an average decrease of -38 +/- 4.3 mmHg in ABP (N = 6). Ten min after bilateral microinjection of the broad-spectrum glutamate antagonist kynurenic acid (KYN, 2 nmol 200 nl-1 site-1) into the caudal ventrolateral medulla (CVLM) depressor responses to CPA inhibition were virtually abolished (-3 +/- 1.7 mmHg, P < 0.05). Similar microinjection of KYN into the rostral ventrolateral medulla (RVLM) or into the CPA itself did not modify depressor responses to CPA inhibition by glycine. 3. CPA stimulation by bilateral microinjection of the excitatory amino acid L-glutamate (L-glu, 50 nmol 200 nl-1 site-1) produced an increase in ABP (+43 +/- 5.4 mmHg, N = 6). Bilateral microinjection of the GABAA antagonist bicuculline methiodide (BIC, 200 pmol 200 nl-1 site-1) into the CVLM markedly reduced pressor responses to CPA stimulation (+6 +/- 2.7 mmHg, P < 0.05). Similar application of BIC into the RVLM or CPA did not modify pressor responses to CPA stimulation by glutamic acid.

Putative pathways involved in cardiovascular responses evoked from the caudal pressor area

1. The caudal pressor area (CPA) is a recently identified site within the ventrolateral medulla which is involved in cardiovascular regulation. CPA chemical stimulation by L-glutamate produces an increase in arterial blood pressure (ABP) while its inhibition by GABA or glycine evokes marked hypotension. In the present study, we sought to determine the potential neural pathways underlyng these responses. 2. In urethane-anesthetized, paralyzed, artificially ventilated rats, CPA inhibition by bilateral microinjection of the inhibitory amino acid glycine (Gly, 100 nmol 200 nl-1 site-1) produced an average decrease of -38 + or - 4.3 mmHg in ABP (n = 6). Ten min after bilateral microinjection of the broad-spectrum glutamate antagonist kynurenic acid (KYN, 2 nmol 200 nl-1 site-1) into the cauldal ventrolateral medulla (CVLM) depressor responses to CPA inhibition were virtually abolished (-3 + or - 1.7 mmHg, P<0.05). Similar microinjection of KYN into the rostral ventrolateral medulla (RVLM) or into the CPA itself did not modify depressor responses to CPA inhibiton by glycine. 3. CPA stimulation by bilateral microinjection of the excitatory amino acid L-glutamate (L-glu, 50 nmol 200 nl-1 site-1) produced an increase in ABP (+43 + or - 5.4 mmHg, N= 6). Bilateral microinjection of the GABA A antagonist bicuculline methiodide (BIC, 200 pmol 200 nl-1 site-1) into the CVLM markedly reduced pressor responses to CPA stimulation (+6 + or - 2.7 mmHg, P<0.05). Similar application of BIC into the RVLM or CPA did not modify pressor responses to CPA stimulation by glutamic acid