The occurrence and distribution of certain polypeptides within the human carotid body

Summary Both carotid bodies from 26 patients coming to necropsy were fixed in 10% neutral buffered formalin and sections 4 m thick were stained for various peptides by use of the immunogold technique. The results show that the human carotid body contains met- and leu-enkephalin, substance P, vasoactive intestinal peptide (VIP), neurotensin and bombesin. The distribution of these six peptides within the carotid body differs. Thus met- and leu-enkephalin are both present predominantly within glomic chief cells but with a marked tendency to favour the dark variant of these cells. Substance P and VIP both show a weak immunoreactivity in comparison to the enkephalins and are present in all three variants of chief cell. Neurotensin shows the weakest immunoreactivity of all and is restricted to a few glomic chief cells in a minority of cases. Bombesin also shows a weak immunoreactivity in glomic chief cells but a strong reaction in glomic arteries and arterioles. In these vessels bombesin appears to be confined to smooth muscle cells in the media but we cannot say whether it is secreted by them or merely bound to receptor sites on their membranes. These findings are related to quantitative data on the concentration of peptides in the human carotid body from a previous paper with which we were associated.     

Ontogeny of substance P-, CGRP-, and VIP-containing nerve fibers in the amphibian carotid labyrinth of the bullfrog,Rana catesbeiana

Summary The ontogeny of substance P, CGRP (calcitonin gene-related peptide), and VIP (vasoactive intestinal polypeptide) containing nerve fibers in the carotid labyrinth of the bullfrog, Rana catesbeiana, was examined by the peroxidase-antiperoxidase method. The time of appearance of these three peptides was different for each. First, CGRP fibers appeared in the wall of the carotid arch and external carotid arteries, and in a thin septum between these two arteries at an early stage of larval development (stage III). At stage V, substance P immunoreactive fibers appeared, and VIP fibers were detected at the early metamorphic stage (stage XXII). Up to the completion of metamorphosis, the number of these fibers remained low. From 1 to 5 weeks after metamorphosis, substance P, CGRP, and VIP fibers increased in number to varying degrees. By 8 weeks after metamorphosis, the distribution and abundance of these fibers closely resembled those of the adults. Some CGRP and VIP immunoreactive glomus cells were found at the stages immediately before and after the completion of metamorphosis. These findings suggest that substance P, CGRP, and VIP fibers during larval development and metamorphosis may be nonfunctional, and start to participate in vascular regulation only after metamorphosis. The transient CGRP and VIP in some glomus cells may be important for the development of the labyrinth, or may take part in vascular regulation through the close apposition of the glomus and smooth muscle cells (g-s connection).     

Biogenic Amine-Stimulated Cyclic Adenosine-3'',5''-Monophosphate Formation in the Rat Carotid Body

The subcutaneous injection of isoprenaline, salbutamol, histamine, and adrenaline to rats, which were subsequently killed by microwave irradiation, resulted in a rapid increase in the cyclic AMP content of the carotid body. On the other hand, noradrenaline, dopamine, adenosine, and 5-hydroxytryptamine, at doses at least 100 times greater than that of isoprenaline, did not significantly alter the cyclic nucleotide content in vivo. The response to isoprenaline was dose related, with an ED50 of 15 micrograms X kg-1, and reached a peak level 1-1.5 min after injection. Incubation of intact carotid bodies with isoprenaline (10(-5) M) in vitro also resulted in a 10-fold increase in cyclic AMP content. The in vivo response to isoprenaline could be blocked stereo-selectively by propranolol, and ICI 118.551, a beta 2-selective antagonist, blocks the isoprenaline-elicited increase in cyclic AMP completely at a dose of 30 micrograms X kg-1; whereas betaxolol, a beta 1-selective antagonist, was ineffective, even at a dose of 300 micrograms X kg-1. Hypoxia (5% oxygen in 95% N2) did not result in a significant increase in the cyclic AMP content, nor did it significantly alter the isoprenaline-stimulated increase in the cyclic AMP content of the rat carotid body. These results suggest that some catecholamines may stimulate cyclic AMP formation by interacting with a beta 2-adrenoceptor in the rat carotid body.     

Nitric oxide synthase in the rat carotid body and carotid sinus

The participation of nitric oxide synthase (NOS) in the innervation of the rat carotid body and carotid sinus was investigated by means of NADPH-diaphorase histochemistry and NOS immunohistochemistry using antisera raised against purified neuronal NOS and a synthetic tridecapeptide. NOS was detected in 23% of neurons at the periphery of the carotid bodies. Some negative neurons were surrounded by NOS-positive terminals. NOS-containing varicose nerve fibres innervated the arterial vascular bed and, to a lesser extent, the islands of glomus cells. These fibres persisted after transection of the carotid sinus nerve and are probably derived from intrinsic neurons. Large NOS-positive axonal swellings in the wall of the carotid sinus were absent after transection of the sinus nerve, indicating their sensory origin. The results suggest a neuronal nitrergic control of blood flow, neuronal activity and chemoreception in the carotid body, and an intrinsic role of NO in the process of arterial baroreception.     

Localization of cholecystokinin-like and calcitonin-like peptides in infant carotid bodies: a light- and electron-microscopic immunohistochemical study

Previous immunohistochemical studies have identified several regulatory peptides in the carotid body chief cells in both humans and animals. These peptides, together with amines, may be important in the modulation of the chemoreflex by the carotid body. We report the localization and distribution of calcitonin and cholecystokinin-like (CCK) immunoreactivity in chief cells of human infant carotid body by light- and electron-microscopic immunohistochemical techniques. Consecutive sections immunostained with calcitonin and/or CCK antibodies revealed positively stained chief cells, both alone and in clusters, scattered throughout the carotid body lobule. Generally more chief cells were positive for calcitonin than for CCK. This was confirmed by quantiative analysis showing that the ratio of calcitonin to CCK immunoreactive cells was consistently >2:1 in all cases studied. There was no apparent correlation between the immunoreactivity for the two peptides and the age, sex, or postmortem interval. Calcitonin-like and CCK-like immunoreactivities were localized electron-microscopically over the dense core granules of the chief cells. Calcitonin and CCK-like peptides in carotid body chief cells may act as neutransmitters or neuromodulators involved in chemoreception.     

高血压前期患者颈动脉血管弹性超声参数与左室舒张功能的关系研究

摘要 目的：研究高血压前期患者颈动脉血管弹性超声参数与左室舒张功能的关系。方法：选取2019年12月-2020年12月因血压异常于河北北方学院附属第一医院接受诊断与治疗的161例患者,根据血压水平分为高血压前期组（82例）与高血压组（79例）;另选取同期于我院体检的80例健康志愿者作为对照组。收集三组临床资料,检测生化指标与血压;通过超声诊断仪中超声射频信号血管内中膜定量分析（QIMT）与动脉僵硬度定量分析（QAS）软件测量颈动脉血管弹性超声参数[颈动脉内中膜厚度（IMT）、顺应性系数（CC）、扩张性系数（DC）、血管弹性指数（α、β）、脉搏波传导速度（PWV）];超声心动图检查左室功能指标[左室射血分数（LVEF）、左室质量指数（LVMI）、舒张早期血流速度峰值（E）/舒张晚期血流速度峰值（A）、等容舒张时间（IVRT）、舒张期减速时间（DT）];采用Pearson相关性法分析颈动脉血管弹性超声参数与心室指标的相关性。结果：三组收缩压与舒张压水平存在统计学意义（P＜0.05）。高血压前期组与高血压组IMT、α、β、PWV高于对照组,DC、CC低于对照组（P＜0.05）,且高血压前期组IMT、α、β、PWV低于高血压组,DC、CC高于高血压组（P＜0.05）。高血压前期与高血压组E/A低于对照组,IVRT、DT高于对照组（P＜0.05）,且高血压前期组E/A高于高血压组,IVRT、DT低于高血压组（P＜0.05）。经Peason相关性分析显示,IMT、α、β、PWV与E/A呈负相关,与IVRT、DT呈正相关（P＜0.05）;DC、CC与E/A呈正相关,与IVRT、DT呈负相关（P＜0.05）。结论：高血压前期患者颈动脉血管弹性功能下降,且伴有左室舒张功能受损,颈动脉血管弹性超声参数与左室舒张功能密切相关。     

Effects of intracerebroventricular administration of aminophylline on hyperbaric-induced increase in carotid blood flow

Carotid blood flow was measured in rats by implanted transit-time ultrasonic flowprobes during hyperbaric experiments at up to 70 bar (7 MPa) using an helium-oxygen hyperoxic (partial pressure of O₂ = 400 mbar) mixture. Before the hyperbaric experiment, an intracerebroventricular injection of phosphate saline buffered solution (PBS) or aminophylline, an adenosine receptor blocker, in PBS was given. Throughout the hyperbaric experiment carotid blood flow increased with ambient pressure in both PBS, i.e. control, and aminophylline treated rats. The increase in carotid blood flow was significantly attenuated in aminophylline treated rats. Additional experiments showed that the increased carotid blood flow was independent of hyperoxia as well as of temperature. The hypothesis that the hyperbaric dependent increase in carotid blood flow was mediated by brain adenosine receptors and its implication regarding a cerebral vasodilatation are discussed.     

Morphometric analysis of atrial natriuretic peptide-containing granules in atriocytes of rats with experimental congestive heart failure

The morphometric characteristics of atrial natriuretic peptide-containing granules were studied in atrial myoendocrine cells of rats with aorto-caval fistula, an experimental model of congestive heart failure. A total of 6680 granules of control and aorto-caval rats were analyzed by a computerized image analysis system that evaluated the number and sectioned surface area of granules and their subcellular location. Compared with control animals, rats with congestive heart failure displayed a slight increase in the number of peripheral granules, adjacent to the sarcolemma, but not centrally located in the Golgi areas. The mean sectioned surface area of granules in rats with congestive heart failure was about 50% of that in controls, both in the right and left atria. Rats with aortocaval fistula had a higher percent of small granules and lower percent of large granules compared with controls. The data demonstrate different morphometric characteristics in atrial natriuretic peptide-containing granules in atriocytes in rats with experimental congestive heart failure; this may reflect the enhanced synthesis and release of atrial natriuretic peptide in heart failure.     

Analysis of food stimulation of gastrin release in dogs by a panel of inhibitors

The release of gastrin into the serum of five conscious gastric fistula dogs after a meat meal was monitored for 2 hours. Neither the rate of increase in serum gastrin nor the 2 hour cumulative integrated gastrin response was changed by administration of small doses of somatostatin tetradecapeptide (0.5 microgram/kg.hr IV for 2 hr), 16-16 dimethyl prostaglandin E2 (0.25 microgram/kg.hr IV for 2 hr or 1 microgram/kg intragastrically), or bethanechol (20 micrograms/kg.hr IV for 2 hr). Acidification of the food in the antrum to pH 1.2 to 1.4 eliminated serum gastrin release in response to food. In control studies, serum gastrin levels were not altered by IV administration of saline for 2 hr with no food or when a plate of food was held just out of the dogs' reach (teasing). Food-stimulated gastrin release was contrasted with that stimulated by bombesin under identical laboratory conditions [17]. In each case, antral acidification, somatostatin, prostaglandin E2 and bethanechol affected bombesin-stimulated gastrin release differently from that stimulated by food. We conclude that food and bombesin release gastrin by different pathways.