The carotid bodies of renal hypertensive rats

The carotid bodies of renal hypertensive rats (one kidney wrap model) were studied by light-microscopic and morphometric methods. Rats with established hypertension showed massive intraglomic vascular alterations, such as exudation of plasma, subendothelial fibrinoid deposits and fibrinoid necroses of the intima and media. Additionally a granuloma-like perivascular proliferation of fibroblasts and histiocytes was seen. The total carotid body volume was enlarged but the volume of the specific glomic tissue was reduced in comparison with normotensive controls. In rats with borderline hypertension similar pathological changes were found but in a more reduced extension. Additionally in these rats some intraglomic vessels showed an accumulation of acid mucopolysaccharides and an hyperplasia of mediocytes. Rats with such vessel alterations also exhibited a small enlargement of specific glomic tissue. In general the pathological changes of the carotid bodies in renal hypertensive rats are different in comparison with those in the glomera carotici of rats with spontaneous hypertension (SHR, GH rats). This study suggests that an elevated blood pressure does not solely cause an increment of the specific chemoreceptive tissue mass of the carotid bodies.     

The aortic bodies of spontaneously hypertensive (SHR) and normotensive rats--a study concerning location and size

The aortic bodies, including the right and left subclavian bodies and the superior aorticopulmonary bodies, were examined in inbred normotensive control rats (NCR) of the Wistar strain and in spontaneously hypertensive rats (SHR) of the OKAMOTO-AOKI strain. Paraganglia were found in all rats of either group. They were located near to the left common carotid artery and less frequently between the branching right subclavian and right common carotid artery. Superior aorticopulmonary bodies were rarely seen. No significant differences were found regarding the volume of individual aortic bodies when comparing these paraganglia in NCR and SHR. However, aortic bodies are more numerous in SHR and therefore the total volume of aortic body tissue per rat is significantly larger in this strain. There was good correlation between the total volume of aortic bodies and the total volume of carotid bodies in both strains of rats studied. These findings indicate, that the paraganglionic system as a whole is enlarged in SHR. This enlargement probably is caused genetically and not a result of increased blood pressure.     

Morphological findings at the carotid bodies of humans suffering from different types of systemic hypertension or severe lung diseases

Post-mortem studies of the carotid bodies of 62 humans were carried out using light microscopic and morphometric methods. According to the clinical and autopsic data the subjects were divided into 5 groups: normotensives, essential hypertensives, renal hypertensives, chronically hypoxic persons with severe lung diseases, and people who suffered from both lung diseases and essential hypertension. Carotid body volume showed age-dependence in the normotensive group; the biggest glomera carotici were found at an age of 40-60 years, whereas younger and older people exhibited smaller carotid bodies. In the group with the essential hypertensives only old patients exhibited enlarged carotid bodies. In younger essential hypertensives but also in the renal hypertensives an increase of carotid body size was not demonstrable. The people with severe lung diseases regularly had greater carotid bodies when compared with age-matched normotensive subjects. In addition, chronically hypoxic patients had a proliferation of type II cells, perhaps with involvement of Schwann cells and fibrocytes. This increases of elongated cells was only seldom observed in the other groups. The results are discussed with respect to the alterations known so far of arterial chemoreceptor function and reflex effects in systemic arterial hypertension.     

Arteriovenous anastomoses at the carotid bodies of rats

In 2 out of 390 carotid bodies of rats arteriovenous anastomoses (AVA) have been found. Both cases belonged to a group of 12 glomera carotici which were prepared using the semithin section technique. The AVA were found in the course of branches of the glomic arteries leaving the main vessel before its entrance into the carotid body tissue. Thus the AVA were placed near but outside of the carotid bodies. Histologically they showed a distinct extension of the tunica media caused by epitheloidly modified smooth muscle cells. Functionally these AVA could act as shunt vessels (Sperrarterien) that would be able to control the blood flow and/or flow distribution through their carotid bodies.     

Inhibition of renal sympathetic nerve traffic from cardiac receptors in normotensive and spontaneously hypertensive rats

The reflex inhibition of the sympathetic outflow to the kidney was examined during volume load with horse plasma in 6 normotensive rats (NCR) and 6 spontaneously hypertensive rats (SHR). The rats were anesthetized with chloralose and urethane. The arterial baroreceptors were denervated. The renal nervous inhibition was mediated via the vagal nerves and was mainly due to activation of receptors in the left side of the heart. The average thresholds in mean left atrial pressure for renal nervous inhibition was 5.4 mmHg for NCR and 9.2 mmHg for SHR indicating a clear resetting of the reflex arch in the hypertensive animal: The reason is probably a decreased distensibility of the wall of the left atrium due to a chronic elevation of left atrial pressure. This resetting of the atrial receptors in the hypertensive animals is probably of importance to allow an adequate filling pressure of the hypertrophied left ventricle and might also be of importance for the reflex neural control of renal function in these animals.     

Sodium balance during development of hypertension in the spontaneously hypertensive rat (SHR)

Sodium balance was studied in 7 and 16 week old male spontaneously hypertensive rats (SHR), in matched normotensive Wistar rats (NCR) and in Wistar Kyoto rats (WKR). The animals were placed in metabolic cages and given diets with either normal sodium content (5.35 mmol sodium/100 g food) or with a sodium content 3 or 10 times the normal. Whether on normal or increased sodium diet we did not observe any increased sodium retention in either SHR age group. However, in both SHR groups urinary sodium excretion was significantly decreased, while faecal sodium excretion was correspondingly increased compared with the controls. This shift of sodium excretion from kidneys to gastrointestinal tract in SHR did not reflect any ‘primary’ inability of the SHR kidneys to excrete sufficient sodium amounts since on high sodium diet they excreted the increased sodium load as readily as the normotensive controls. The present results do not support the concept that a primary renal retention of sodium and water should be of pathogenetic importance for the SHR variant of primary hypertension.     

Inhibition of renal sympathetic nerve traffic from cardiac receptors in normotensive and spontaneously hypertensive rats.

The reflex inhibition of the sympathetic outflow to the kidney was examined during volume load with horse plasma in 6 normotensive rats (NCR) and 6 spontaneously hypertensive rats (SRH). The rats were anesthetized with chloralose and urethane. The arterial baroreceptors were denervated. The renal nervous inhibition was mediated via the vagal nerves and was mainly due to activation of receptors in the left side of the heart. The average thresholds in mean left artrial pressure for renal nervous inhibition was 5.4 mmHg for NCR and 9.2 mmHg for SHR indicating a clear resetting of the reflex arch in the hypertensive animal: The reason is probably a decreased distensibility of the wall of the left atrium due to a chronic elevation of left atrial pressure. This resetting of the atrial receptors in the hypertensive animals is probably of importance to allow an adequate filling pressure of the hypertrophied left ventricle and might also be of importance for the reflex neural control of renal function in these animals.     

The paraganglia within the carotid bifurcation regions of young and old spontaneously hypertensive rats (SHR) after exposure to chronic hypobaric hypoxia. I. The carotid bodies

Carotid body volumes and the histological appearance of these chemoreceptors were studied using light microscopic methods in 10 groups of spontaneously hypertensive rats (SHR). The aim of this study was to clarify the influence of chronic hypobaric hypoxia on the carotid bodies of SHR depending on the age of the rats, on the duration of exposure to hypoxia, and on different salt intake, respectively different blood pressure. We found that: 1. The carotid bodies of chronically hypoxic SHR are enlarged. 2. The degree of carotid body enlargement is dependent on the duration of exposure to hypoxia. 3. In old SHR the increase of carotid body volume was smaller than in young SHR. 4. Old chronically hypoxic SHR exhibited more distinct vascular changes in the carotid bodies than age-matched normoxic controls as well as younger chronically hypoxic and normoxic SHR. 5. The influence of different levels of systemic arterial blood pressure on the carotid body volumes was rather small compared with the effects of chronic hypobaric hypoxia.     

Cardiovascular Responses to Acute Mental ‘Stress' in Spontaneously Hypertensive Rats

Spontaneously hypertensive rats (SHR), aged 7 months (‘manifest’ hypertension) or 10–11 weeks (‘prehypertensive’), and renal hypertensive rats (RHR; ‘nonhereditary’ hypertension were compared with normotensive rats (NCR) concerning cardiovascular responses to mental ‘stress’. Blood pressure and heart rate were followed in pairs of awake SHR—NCR and RHR—NCR, while defence reactions were provoked by alerting stimuli (light, noise, vibrations). The tachycardia, here involving both accentuated sympathetic and centrally suppressed vagal discharge, reflected the intensity of neural activation and the pressuie rise the imposed load on heart and vessels. In both respects the SHR groups responded decidedly stronger than NCR and RHR, also after either adrenergic or vagal cardiac blockade. Since SHR and NCR hearts responded equally to graded vagal stimulations or to isoprenaline, the enhanced tachycardia responses reflected a truly intensified defence reaction in SHR. Further, SHR responded more often to mild stimuli than NCR, suggesting a lower ‘threshold’ for defence reactions, and more frequently with clearcut defence reactions than NCR which exhibited vagal bradycardia responses in 30 %, versus 5 % in SHR. This hyperreactivity and apparent prevalence concerning ‘sympathotonic’ patterns in SHR during alertness, in turn tending to trigger structural vascular adaptation and manifest hypertension, is evidently genetically linked and not secondary to hypertension, being observed particularly in ‘prehypertensive’ SHR but not in RHR.     

Further evidence for abnormal hindquarter tone in spontaneously hypertensive rats

In spontaneously hypertensive rats (SHR) and normotensive control rats (NCR), hindquarter flow was observed in the conscious state with an electromagnetic flow probe chronically implanted around the terminal aorta. Arterial pressure was recorded with an indwelling catheter in the common carotid. When arginine vasopressin was infused intravenously at a rate of 12.5 ng/(kg.min), the increase in hindquarter resistance, calculated as arterial pressure divided by hindquarter flow, was significantly (p less than 0.005) augmented after ganglionic blockade with hexamethonium in SHR but not in NCR. This is explicable by assuming a tonic sympathetic vasoconstrictor activity in the hindquarters of SHR, reflexive inhibition of which partially offsets vasoconstrictor effect of infused vasopressin.     

Contractility,Muscle Mass and Agonist Sensitivity of Isolated Portal Veins from Normo- and Hypertensive Rats

Properties of the longitudinal smooth muscle of portal veins from normotensive Wistar rats, adult (NCR) and young (NCR_y); spontaneously hypertensive Okamoto rats, adult (SHR) and young (SHR_y); and adult Wistar rats with renal hypertension (RHR) were studied in vitro and histologically. Some aortic strips from SHR and SHR_y were compared with controls. In response to noradrenaline (NA) and acetylcholine (ACh) greater maximum force was developed by veins from all hypertensive groups than by those from control rats. Cross-sectional area of the longitudinal muscle of veins from SHR but not SHR nor RHR was greater than control. Maximum stress in response to agonists was greater in both SHR and RHR than NCR. ED_so-values for NA and ACh were lower in portal veins from SHR than NCR but not from RHR nor SHR_y compared to controls. Denervation did not abolish any of the differences between SHR and NCR. Aortic strips from SHR developed less maximum force to NA and ED₅₀ was greater than those from NCR. i.e. opposite to the findings in portal veins. Low levels of external Ca^2- reveal altered calcium handling in veins from SHR compared to controls. It is concluded that portal veins from hypertensive rats are functionally different from those of normotensive rats and differ in SHR compared to RHR. It is suggested that the altered functional properties of portal vein, but not of aorta, in several respects resemble those of arterial resistance vessels. The implications of these findings are discussed in terms of mechanisms of hypertension in these animal models.     

Postnatal oxytocin treatment of spontaneously hypertensive male rats decreases blood pressure and body weight in adulthood

Postnatal oxytocin treatment decreases blood pressure and increases body weight in adult normotensive rats. The aim of the present study was to investigate the effect of postnatally administered oxytocin on blood pressure, heart rate and body weight in spontaneously hypertensive rats (SHR). For this purpose SHR male pups were given oxytocin (1 mg/kg) or saline subcutaneously once a day on days 10-14 after birth. Blood pressure and heart rate were measured at the age of 2 months. Weight was registered continuously. The postnatally oxytocin-treated male SHR had significantly lower systolic blood pressure as adults compared to the controls (158 vs. 169; p<0.05). They also had a tendency to lower diastolic blood pressure (119 vs. 128; p=0.10). Heart rate was equal in the two groups. The postnatally oxytocin-treated male SHR had a significantly lower body weight at the age of 5-8 weeks compared to the controls (ANOVA p=0.014).     

Evidence for an antihypertensive factor from the adrenal medulla of SHR modulating neurogenic vasoconstriction

The aim of this study is to investigate some vasoactive properties of the blood of spontaneously hypertensive rats (SHR). Isolated segments of rat tail arteries obtained from normotensive rats (Wistar-Kyoto (WKY) and Wistar) were perfused with blood from conscious donor rats (WKY, Wistar or SHR). Alterations of the neurogenic constrictor responses (NCR) of the isolated segments evoked by electrical stimulation were studied. The amplitude of NCR of the isolated arteries was studied during perfusion with blood according to the perfusion scheme WKY1(1)-SHR1(2)-WKY1(3) and WKY1(1)-WKY2(2)-WKY1(3). The release of 3H-noradrenaline ([3H]-NA) from vascular sympathetic fibres was measured. The influence of adrenal demedullation on NCR was estimated. We have shown that NCR of isolated arteries decreased by 28.3 +/- 7.9% (P < 0.05 vs. WKY1(1)) during perfusion with blood from SHR (scheme WKY1(1)-SHR1(2)-WKY1(3)). In these experiments, release of [3H]-NA from sympathetic fibres of the artery segments decreased by 39.9 +/- 9.6% during the perfusion with blood from SHR vs. WKY1(1) (P < 0.05). Adrenal demedullation prevented the decrease of NCR during perfusion of the arteries with blood from SHR. In conclusion, the blood of SHR has some antihypertensive factor(s), which causes decrease of NCR in the tail artery from normotensive rats. This decline is accompanied by the decrease of release in [3H]-NA from the transmural sympathetic fibres and is abolished after adrenal demedullation of blood donor rats.     

Increase in body weight of spontaneously hypertensive rats (SHR) under prolonged behavioral stimulation

We noticed that during 44 weeks of exposure to a number of behavioral tests (such as assessments of emotionality, locomotion, short term memory and visual discrimination learning) the body weight of spontaneously hypertensive rats (SHR) increased above that of normotensive controls (NT). To determine whether this difference was related to "behavioral stimulation" resulting from different testing situations and accompanying handling, body weights were recorded in other SHR and NT groups not subjected to any experiment (unstimulated). Stimulated SHR were significantly heavier than rats from other subgroups (unstimulated SHR as well as stimulated and unstimulated NT rats) which did not differ from one another. The first significant difference appeared after 7 weeks of behavioral training (18th week of life). Several weeks later, and continuing for the duration of study, stimulated SHR were approximately 12% heavier than the other 3 groups. No effect of behavioral testing on blood pressure was seen in either strain.     

Comparison of the Somatosympathetic Reflex in Normotensive and Spontaneously Hypertensive Rats

Acute experiments under chloralose anaesthesia were performed in normotensive (Wistar and Wistar-Kyoto) and hypertensive (SHR) rats for recording of electrical discharge in the upper cervical sympathetic stem in response to stimulation of afferent fibers of the median nerve of the forelimb. These experiments showed that the evoked response was of the same shape in hypertensive rats as in normotensive rats. The latent period, duration of each discharge, and spectral characteristics of the somatosympathetic reflex were identical in animals of all the lines studied, though the amplitude of the reflex was greater in SHR rats than in normotensive animals. It is suggested that the organization of the somatosympathetic reflex is identical in hypertensive and normotensive rats. The reflex excitability of the sympathetic nervous system was increased in SHR rats.     

Morphology of the carotid sinus wall in normotensive and spontaneously hypertensive rats

The morphology of the carotid sinus region of the internal carotid artery was studied in spontaneously hypertensive rats (SHR) at 5, 8, 16, and 24 weeks of age. The carotid sinus region occupied the proximal millimeter of the internal carotid artery, and was easily recognizable by the presence of an extensive adventitial capillary plexus, which was absent on adjacent arteries (e.g., common and external carotid arteries). Methylene blue-stained whole-mount preparations showed the extent of baroreceptor nerves over the sinus. Baroreceptor fibers terminated in distinctive bulbous-like endings, which, at the ultrastructural level, were filled with mitochondria. No differences were noted in the sinus adventitial capillary network or baroreceptor distribution between SHR and age-matched Wistar-Kyoto (WKY) normotensive control animals. With the onset of a significant rise in SHR blood pressure, the carotid sinus wall increased in thickness and total vessel size. The wall/lumen ratios were significantly larger in the SHR than in age-matched WKY ratios in all age groups. SHR carotid sinus vessel enlargement was uniform throughout the vessel tunics, with no significant change in the proportion of the tunica media occupied by smooth muscle cells. The increase in the carotid sinus wall thickness associated with increasing hypertension could affect the ability of the sinus to distend and may play a secondary role in the maintenance of hypertension by compromising baroreceptor nerve ending sensitivity.     

Effects of ageing on cardiac performance and coronary flow in spontaneously hypertensive and normotensive rats

The aim of the present study was to assess the influence of ageing on cardiac function and coronary flow in Wistar Kyoto normotensive rats (WKY, 16 and 78 weeks of age) and spontaneously hypertensive rats (SHR) of the same age. Cardiac function was determined on isolated hearts by means of an antegrade heart perfusion technique. Left atrial pressure and peak aortic pressure could be altered independently of each other. Recordings of cardiac output and coronary flow were then obtained at both normotensive and hypertensive levels of peak aortic pressures. Peak stroke volume (SV) was reduced with age in both WKY and SHR. Peak SV determined at normotensive pressure loads became diminished with age in WKY, while it at hypertensive pressure loads showed a small decline with age, since peak SV was low as early as 16 weeks of age. The age-dependent fall in cardiac performance was greater in SHR than in WKY, due to the enhanced peak SV in 16-week-old SHR at hypertensive pressure loads. Peak SV was markedly decreased at normotensive pressure levels in both 16- and 78-week-old SHR v. age-matched WKY. Coronary flow per unit tissue declined with age both in WKY and SHR. Coronary flow was also lower in SHR compared to age-matched WKY. With ageing this elevated performance was reduced down to the same level as in 78-week-old WKY. The age-related coronary flow reduction and the consistently reduced flow in SHR indicate a structural narrowing of the coronary vascular bed, particularly in SHR.     

Modification of aortic barorecptor resetting in the spontaneously hypertensive rat.

Aortic barorecptor function was studied in spontaneously hypertensive rats (SHR) of various ages and normotensive Wistar rats. The aortic arch was isolated and perfused, and the activity of the left aortic nerve was recorded. The threshold pressure to elicit barerecptor firing was 80-120 mmHg in normotensive Wistar rats. Resetting of barorecptors (threshold pressure 160-180 mmHg) was found in all untreated SHR of 35-70 wk of age. Resetting of barorecptors was prevented in SHR by starting treatment with antihypertensive agents at the age of 11 wk. Treatment of 32-wk old SHR with antihypertensive agents for 4-6 wk resulted in reversal of barorecptor resetting in 50% animals. The percentage of SHR showing complete reversal of resetting did not increase even when the duration of treatment was tripled. In 52- to 64-wk old SHR, treated with antihypertensive agents, reversal of baroceptor resetting was seen in only 30% animals. It was concluded that baroceptor resetting in SHR was secondary to hypertension. Hypertension, in turn, induced hypertrophy of the tunica media of the aorta. Histological studies showed a close correlation between aortic hypertrophy resetting. Aortic hypertrophy may, therefore, be one of the important factors involved in baroceptor resetting.     

Consequence of social isolation on blood pressure, cardiovascular reactivity and design in spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR), which inherently display exaggerated cardiovascular defence reactions to environmental stimuli (Hallb?ck and Folkow 1974), and normotensive control rats (NCR) were kept isolated after they were weaned to reduce such environmental influences which normally induce psychological activation. Mean arterial pressure was followed until 7 months of age, when the cardiovascular defence reactions to acute mental stress were compared and an analysis of cardiovascular design was made. The isolated SHR but no the isolated NCR, had significantly lower pressures than their unisolated controls. Likewise, judged by the relative weight of the left ventricle and the hemodynamically evaluated design of the hindquarter resistance vessels, the structural cardiovascular adaptation was about proportionally less pronounced in isolated than in control SHR. However, their cardiovascular responses to acute "psychological stress" were equally intense, and clearly exaggerated when compared with NCR. Thus, a prolonged reduction of excitatory environmental influences implies a relatively less pronounced development of hypertension in SHR, even though an inherent hyperreactivity concerning neurohormonal pressor responses to alerting stimuli is present. These findings tress the importance of interacting intrinsic-hereditary and extrinsic neurogenic influences for the initiation of primary hypertension.     

A comparison of the blood supply of the carotid body in rats and rabbits

Light-microscopic findings regarding the arterial blood supply of the carotid bodies in 145 Wistar rats, in 175 spontaneously hypertensive rats (SHR) and in 14 rabbits were compared. In rats, only one glomic artery was found in each of 637 carotid bifurcations. In 2 bifurcations 2 carotid body arteries supplied the glomus caroticum, the glomic artery being of the muscular type. At the origin of the carotid body artery almost regularly intraarterial cushions were observed in rats. They were also demonstrable at the origin of first or second order branches of the glomic artery. Concerning the origin of the carotid body artery as well as presence and form of the intraarterial cushions some differences between the 2 strains of rats studied were detected. In rabbits the glomic artery was of the elastic type. In 2 out of 28 carotid bifurcations 2 carotid body arteries were found. In all other cases the glomus caroticum was supplied by one artery only. The glomic artery did not terminate in the glomus caroticum in rats as well as in rabbits. Many similarities between the light-microscopic picture of the internal carotid artery and the carotid body artery were observed in rabbits. Therefore a baroreceptor function of the glomic artery seems to be possible.