Neurochemical plasticity of the carotid body in hypertension

Abstract

The carotid body (CB), a main peripheral arterial chemoreceptor, has lately been implicated in the pathophysiology of various cardiovascular disorders. Emerging experimental evidence supports a causal relationship between CB dysfunction and augmented sympathetic outflow which is the common hallmark of human sympathetic‐related diseases, including essential hypertension. To gain insight into the neurotransmitter profile of chemosensory cells in the hypertensive CB, we examined the expression and cellular localization of some classical neurotransmitters, neuropeptides, and gaseous signaling molecules as well as neurotrophic factors and their receptors in the CB of spontaneously hypertensive rats, a common animal model of hypertension. Our immunohistochemical experiments revealed an elevated catecholamine and serotonin content in the hypertensive CB compared to normotensive controls. GABA immunostaining was seen in some peripherally located glomus cells in the CB of SHR and it was significantly lower than in control animals. The density of substance P and vasoactive intestinal peptide‐immunoreactive fibers was diminished whereas that of neuropeptide Y‐immunostained nerve fibers was increased and that of calcitonin gene‐related peptide‐containing fibers remained almost unchanged in the hypertensive CB. We have further demonstrated that in the hypertensive state the production of nitric oxide is impaired and that the components of the neurotrophin signaling system display an abnormal enhanced expression. Our results provide immunohistochemical evidence that the altered transmitter phenotype of CB chemoreceptor cells and the elevated production of neurotrophic factors modulate the chemosensory processing in hypertensive animals which contributes to autonomic dysfunction and elicits sympathetic hyperactivity, consequently leading to elevated blood pressure.

The Human Carotid Body and its Role in Ventilatory Acclimatization to Hypoxia

“…Chronic hypoxia also induces profound changes in other neurochemical systems within the CB such as catecholaminergic, peptidergic and nitrergic systems [23]. Our recent data have indicated that the nitrergic and neurotrophic profile of the CB cell population is also altered in hypertension and this may activate its chemosensitivity [5].…”

The autonomic nervous system from a morphofunctional perspective: Historical overview and current concepts over the last two centuries highlighting contributions from Eastern Europe

“…In this special issue, Dainius Pauza and colleagues from the Lithuanian University of Health Sciences in Kaunas (Lithuania) share their long‐standing expertise and further elaborate on the comparative anatomy of the cardiac and epicardiac innervation as well on the cardiac conducting system validating several models for cardiac research and cardiac pathology (Inokaitis et al, 2023; Pauziene et al, 2023; Saburkina et al, 2023). This part on the autonomic innervation of the heart is further complemented by a review article from Filipovic and collaborators from the University of Split (Croatia) on our current knowledge of the pathophysiological mechanisms and diagnostic approaches related to cardiac autonomic neuropathy (Filipovic et al, 2023), by a joint study from the Bulgarian Academy of Sciences, the Trakia University in Stara Zagora and the Medical University of Sofia demonstrating the neuronal plasticity displayed by the carotid body in hypertension (Atanasova et al, 2023) and by a contribution of Vakhrushev et al (2023) dealing with the significant contribution of ANS dysfunction to the development of cardiovascular diseases such as arterial hypertension, coronary artery disease and chronic heart failure. In most cases the observed symptoms are due to an increase in sympathetic activity and a decrease in parasympathetic activation.…”

Commonalities and differences in carotid body dysfunction in hypertension and heart failure

“…Other similarities between HF and hypertension are the changes in NOS-NO and Ang II-AT 1 R pathways. Atanasova et al (2020Atanasova et al ( , 2022 have demonstrated that SHRs have impaired carotid body NO production with a marked reduction of protein expression for both nNOS and eNOS in both chemoreceptor cells and blood vessels.…”

“…Atanasova et al. (2020, 2022) have demonstrated that SHRs have impaired carotid body NO production with a marked reduction of protein expression for both nNOS and eNOS in both chemoreceptor cells and blood vessels. NO is an essential negative modulator of carotid body activity; it can attenuate its sensory output via either a direct effect on glomus cells or dilatation of blood vessels, thus increasing carotid body blood flow (Brognara et al., 2021; Campanucci & Nurse, 2007; Campanucci et al., 2012; Wang et al., 1993).…”