Carotid body chemoreceptors: physiology, pathology, and implications for health and disease.

The carotid body (CB) is the main peripheral chemoreceptor for arterial respiratory gases O2 and CO2 and pH, eliciting reflex ventilatory, cardiovascular, and humoral responses to maintain homeostasis. This review examines the fundamental biology underlying CB chemoreceptor function, its contribution to integrated physiological responses, and its role in maintaining health and potentiating disease. Emphasis is placed on 1) transduction mechanisms in chemoreceptor (type I) cells, highlighting the role played by the hypoxic inhibition of O2-dependent K+ channels and mitochondrial oxidative metabolism, and their modification by intracellular molecules and other ion channels; 2) synaptic mechanisms linking type I cells and petrosal nerve terminals, focusing on the role played by the main proposed transmitters and modulatory gases, and the participation of glial cells in regulation of the chemosensory process; 3) integrated reflex responses to CB activation, emphasizing that the responses differ dramatically depending on the nature of the physiological, pathological, or environmental challenges, and the interactions of the chemoreceptor reflex with other reflexes in optimizing oxygen delivery to the tissues; and 4) the contribution of enhanced CB chemosensory discharge to autonomic and cardiorespiratory pathophysiology in obstructive sleep apnea, congestive heart failure, resistant hypertension, and metabolic diseases and how modulation of enhanced CB reactivity in disease conditions may attenuate pathophysiology.

Baroreflex responses to electrical stimulation of aortic depressor nerve in conscious SHR.

Baroreflex responses to changes in arterial pressure are impaired in spontaneously hypertensive rats (SHR). Mean arterial pressure (MAP), heart rate (HR), and regional vascular resistances were measured before and during electrical stimulation (5-90 Hz) of the left aortic depressor nerve (ADN) in conscious SHR and normotensive control rats (NCR). The protocol was repeated after beta-adrenergic-receptor blockade with atenolol. SHR exhibited higher basal MAP (150 +/- 5 vs. 103 +/- 2 mmHg) and HR (393 +/- 9 vs. 360 +/- 5 beats/min). The frequency-dependent hypotensive response to ADN stimulation was preserved or enhanced in SHR. The greater absolute fall in MAP at higher frequencies (-68 +/- 5 vs. -38 +/- 3 mmHg at 90-Hz stimulation) in SHR was associated with a preferential decrease in hindquarter (-43 +/- 5%) vs. mesenteric (-27 +/- 3%) resistance. In contrast, ADN stimulation decreased hindquarter and mesenteric resistances equivalently in NCR (-33 +/- 7% and -30 +/- 7%). Reflex bradycardia was also preserved in SHR, although its mechanism differed. Atenolol attenuated the bradycardia in SHR (-88 +/- 14 vs. -129 +/- 18 beats/min at 90-Hz stimulation) but did not alter the bradycardia in NCR (-116 +/- 16 vs. -133 +/- 13 beats/min). The residual bradycardia under atenolol (parasympathetic component) was reduced in SHR. MAP and HR responses to ADN stimulation were also preserved or enhanced in SHR vs. NCR after deafferentation of carotid sinuses and contralateral right ADN. The results demonstrate distinct differences in central baroreflex control in conscious SHR vs. NCR. Inhibition of cardiac sympathetic tone maintains reflex bradycardia during ADN stimulation in SHR despite impaired parasympathetic activation, and depressor responses to ADN stimulation are equivalent or even greater in SHR due to augmented hindquarter vasodilation.

International student exchange and the medical curriculum: evaluation of a medical sciences translational physiology course in Brazil.

The objective of the present study was to conduct a short-term international course on translational physiology for medical students from Wright State University and the University of Iowa. The goals were to 1) provide students with an exposure to the academic, cultural, and medical environments in Brazil; 2) promote awareness of the global medical community; and 3) provide an academic course focused on translational physiology. An evaluation of the students was conducted to determine whether such a short-term course might be useful in the medical curriculum. The 2-wk course was held in the summer of 2005 at the University of São Paulo School of Medicine in Ribeirão Preto, Brazil, for 23 American students. The program included presentations of basic and clinical topics, meetings with medical students, and clinical presentations. The program finished with student attendance at a scientific meeting sponsored by the Brazilian Society of Hypertension. Student surveys evaluated issues related to perceived treatment, Brazilian medical school environment, culture and personal attributes, and career aspirations. The international Medical Sciences Translational Physiology course for medical students provided a brief, but intense, experience. It gave students a picture of the medical environment in Brazil and an appreciation for the differences and similarities in cultures. Most students reported that it was a positive experience that would be beneficial to their careers. In conclusion, a short-term international course provides an efficient means for medical students to experience aspects of global medical science.

Frequency-dependent baroreflex modulation of blood pressure and heart rate variability in conscious mice.

The goal of this study was to determine the baroreflex influence on systolic arterial pressure (SAP) and pulse interval (PI) variability in conscious mice. SAP and PI were measured in C57Bl/6J mice subjected to sinoaortic deafferentation (SAD, n = 21) or sham surgery (n = 20). Average SAP and PI did not differ in SAD or control mice. In contrast, SAP variance was enhanced (21 +/- 4 vs. 9.5 +/- 1 mmHg2) and PI variance reduced (8.8 +/- 2 vs. 26 +/- 6 ms2) in SAD vs. control mice. High-frequency (HF: 1-5 Hz) SAP variability quantified by spectral analysis was greater in SAD (8.5 +/- 2.0 mmHg2) compared with control (2.5 +/- 0.2 mmHg2) mice, whereas low-frequency (LF: 0.1-1 Hz) SAP variability did not differ between the groups. Conversely, LF PI variability was markedly reduced in SAD mice (0.5 +/- 0.1 vs. 10.8 +/- 3.4 ms2). LF oscillations in SAP and PI were coherent in control mice (coherence = 0.68 +/- 0.05), with changes in SAP leading changes in PI (phase = -1.41 +/- 0.06 radians), but were not coherent in SAD mice (coherence = 0.08 +/- 0.03). Blockade of parasympathetic drive with atropine decreased average PI, PI variance, and LF and HF PI variability in control (n = 10) but had no effect in SAD (n = 6) mice. In control mice, blockade of sympathetic cardiac receptors with propranolol increased average PI and decreased PI variance and LF PI variability (n = 6). In SAD mice, propranolol increased average PI (n = 6). In conclusion, baroreflex modulation of PI contributes to LF, but not HF PI variability, and is mediated by both sympathetic and parasympathetic drives in conscious mice.

Qualitative and quantitative morphology of renal nerves in C57BL/6J mice.

The detailed morphology of the renal nerves in mice has not been reported previously. The aims of this study were to describe the general morphology of the extrinsic renal nerve in C57BL/6 mice, and determine its morphometric parameters. The major renal nerve innervating the left kidney was isolated in five mice. Thin sections of the nerve segments were then examined by transmission electron microscopy. The renal nerve averaged 35.4 +/- 3.6 (S.E.M.) microm in diameter and 741 +/- 104 microm in area. The renal nerve contained an average of 830 +/- 169 unmyelinated fibers and only 4.6 +/- 1.7 myelinated fibers. The axon diameter of myelinated and unmyelinated fibers averaged 2.2 +/- 0.3 microm and 0.76 +/- 0.02 microm, respectively. The diameter of the unmyelinated fibers ranged from 0.3 to 2.0 microm, and the distribution histogram was unimodal. The majority of fibers (85%) had diameters of 0.6-1.0 microm. These results are similar to those obtained for renal nerves of rats with respect to the predominance of unmyelinated fibers. However, the diameter of unmyelinated fibers is larger in rats and the distribution histogram of rat unmyelinated fibers is bimodal, in contrast to the unimodal distribution in mice. The morphological description of the renal nerves in mice provides baseline data for further investigations of the structural basis of altered autonomic reflexes. The results will be useful in analyses of genes that influence the development and structure of sympathetic and sensory innervation of the kidney in genetically manipulated mice.