Carotid sinus nerve

Rat carotid sinus nerve activity is diminished by 2-APB during hypoxia (From Roy et al., 2006)... 

Ponte, J. and Sadler, C.I., Studies on the regenerated carotid sinus nerve of the rabbit. J. Physiol Lond., 410, 411 24, 1989. 

This seeming lack of interest of the buffer mechanism to help maintain arterial pressures at normal levels became the subject of study by McCubbin, Green, and myself. The electrical impulses coming from the carotid sinus nerve were measured and it could be shown readily, as others had done, that when pressure within the sinus was raised by intravenous injection of norepinephrine, the impulse traffic to the vasomotor center greatly increased, inhibiting the vasomotor center and reducing the outflow of vasoconstrictor impulses. This led to a decrease in pressure. These observations were in normal dogs. 

According to Douglas and Toh (44), the respiratory stimulation of hydroxytryptamine in dogs is induced reflexly by excitation of chemoceptors, the afferent of which are located in the vagi-aortic and carotid sinus nerves. Experiments of Heymans and van den Heuvel-Heymans (45) showed that intravenous injection of hydroxytryptamine in dogs provoked a marked hyperpnea. This respiratory stimulation is not dependent on stimulation of afferents in the vagi-aortic and carotid sinus nerves. 

Due to its marked variability, it is impossible to state quantitatively whether stimulation by caffeine is affected by sino-aortic denervation. It is clear, however, that good stimulation can be obtained with caffeine in an animal after section of the aortic and carotid sinus nerves. These experiments seem to prove that caffeine acts centrally but they do not eliminate some shght reflex effects by way of the sino-aortic nerves. 

Histologically, three structures can be distinguished in the carotid bodies epithelioid cells, vascular sinuses, and nerve endings. The epithelioid cells are assembled in cords in close contact with the vascular sinuses and with nerve endings. This rich innervation of the epithelioid cells is derived from branches of the carotid sinus nerves, which arise from the glossopharyngeal trunk. The carotid body is activated by severe anoxemia, hypercapnia, and lowered pH. 

Electrical stimulation of the afferent carotid sinus nerve mimicing baroreceptor activation, results in vagal bradycardia and peripheral vasodilation by inhibition of sympathetic discharge. When carotid sinus nerve stimulation is employed in a preparation with the ventricles paced at a constant rate reflex parasympathetic coronary vasodilation is observed in anesthetized (Hackett et ai, 1972 Religa et al., 1972) and unanesthetized preparations (Vatner et al., 1970). However, it is difficult to equate a given nerve stimulation frequency with the carotid sinus pressure that physiologically activates baroreceptors. 

Hagfors, N. R. and Schwartz, S. I., 1966, Implantable electronic carotid sinus nerve stimulators for reducing hypertension, Proc. 19th ACEMB, San Francisco, p. 36. 

The rapid onset of the bradycardia in response to hypoxia is suggestive of a neural reflex (Fig. 2). The sensors for this reflex have been identified as the carotid chemoreceptors (27,28), which send afferent fibers in the carotid sinus nerve to a central integrating area in the brainstem (29) and whose efferent arm consists of parasympathetic cholinergic fibers to the heart carried in the vagus nerve (cranial nerve X) and a-adrenergic sympathetic fibers to resistance vessels in peripheral vascular beds (30). The absence of this bradycardic response earlier in gestation (31) is indicative of immaturity of neural reflex mechanisms. 

Figure 2 Acute fetal responses to hypoxia in the late-gestation sheep fetus. Right-hand graph shows carotid (upper) and femoral (lower) vascular resistance left-hand graph shows fetal heart rate (upper) and perfusion pressure (lower). With intact carotid sinus nerves (O), the normal late-gestation fetal responses to hypoxia are present. When the carotid sinus nerves are out ( ), the initial bradycardia is not seen and there is no early increase in femoral vascular resistance. (From Ref 30.)...

Blessing WW, Yu Y, Nalivaiko E. Medullary projections of rabbit carotid sinus nerve. Brain Res 1999 816 405 10. 

In every species studied to date, the carotid chemoreceptor response to hypoxia increases with postnatal age. In in vitro carotid body preparations, the peak nerve discharge in response to a potent hypoxia stimulus increases about fourfold in neonatal rats during the first month, with most of that change occurring by 2 weeks (10,12,45) (Fig. 2). Similar patterns of postnatal maturation of carotid sinus nerve... 

Tyrosine hydroxylase (TH), a key eirzyme in DA synthesis, also changes during development. An early study of rat carotid body development showed that the level of TH mRNA expression was greatest in the term fetus, decreased 60% by 10 hr postnatal age, and declined another 20% by 4-7 days (54). Similarly, a recent study reported that the level of rat carotid body TH mRNA expression was greatest at birth, significantly decreased by 48 hr postnatal age, and remained decreased at 14 and 21 postnatal days (55). Thus, consistent with the above studies on DA levels, TH mRNA drops rapidly within hours of birth and charrges little during the time frame of carotid sinus nerve activity maturation. 

Fetal sheep carotid sinus nerve (13) and fetal rat type I cell [Ca ]i (68) responses to hypoxia are weak compared to mature postnatal responses. The consensus view is that carotid chemoreceptor O2 sensitivity is suppressed or adapted to the normally low Pa02 of the mammalian fetal environment ( 23-27 mmHg). Nature s design makes sense, from a teleological perspective to disable carotid chemoreceptor... 

Almaraz L, Wang ZZ, Stensaas LJ, Fidone SJ. Release of dopamine fi om carotid sinus nerve fibers innervating type I cells in the cat carotid body. Biol Signals 1993 2(l) 16-26. 

Abbott CP, Daly M de B, Howe A. Early ultrastmctural changes in the carotid body after degenerative section of the carotid sinus nerve in the cat. Acta Anat 1972 83 161-183. 

Mitchell RA, Sinha AK, McDonald DM. Chemoreceptive properties of regenerated endings of the carotid sinus nerve. Brain Res 1972 43 681-685. 

Smith PG, Mills E. Physiological and ultrastructural observations on regenerated carotid sinus nerves after removal of the carotid bodies in cats. Neuroscience 1979 4 2009-2020. 

Stimulate and DA can inhibit cat carotid body neural output. Second, nicotinic, muscarinic, and dopaminergic receptors act in the cat carotid body as they do elsewhere. Thus, exocytotically released ACh and DA should stimulate and inhibit, respectively, postsynaptic neural traffic in the carotid sinus nerve. PresynapticaUy (i.e., on the glomus cells) the presence of the receptors would suggest that—as in other species— they can regulate by positive/negative feedback their own release from the glomus cells and, perhaps, the release of other neurotransmitters. 

Figure 4 In situ recording of neural trafSc in the whole carotid sinus nerve. Cat carotid body is responding to a perfusion of hypoxic Krebs Ringer bicarbonate solution without (open bars) and with (hatched bars) 4 pM AFDX 116, an M2 receptor inhibitor (mean SEM). This neural response could be due to an increase in ACh release because glomus cell M2-inhibiting autoreceptors are inhibited, releasing a greater amount of ACh. Or the postsynaptic M2 receptors (responsible for the slow inhibitory postsynaptic potential) are inhibited, making the postsynaptic sensory afferent neuron more excitable, or both processes.

Figure 5 Effect of chronic hypoxia on the sensitivity of chemoreceptor nerve discharge to specific ETA-receptor antagonist, BQ-123. Left panel shows three superimposed traces of integrated carotid sinus nerve activity in normal rat carotid body separate trace indicates changes in hath PO2. Basal and hypoxia-stimulated nerve activity are minimally altered in the presence of 5pM BQ-123. After 3 days of chronic hypoxia (380torr right panel), nerve activity evoked by acute h5 poxia is substantially reduced in the presence of the drug. (From Ref 9.)...

Figure 8 Integrated antidromic neural activity in the carotid sinus nerve (CSN) and lingual nerve (LN) branches of the glossopharyngeal nerve (IXth n.). Nerve preparation was superfused in vitro. Superimposed traces show that application of a 100-pg bolus (arrows) of ACh to the petrosal ganglion evokes a substantial increase in the CSN and LN nerve discharge, which is inhibited in the presence of 100 pM mecamylamine, a nicotinic receptor antagonist.

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