Left atrial pressure in normotensive and spontaneously hypertensive rats

The left atrial pressure in adult spontaneously hypertensive rats (SHR) of the Okamoto strain and normotensive control rat (NCR) was measured via chronically implanted catheters. In SHR left atrial pressure in end-expiration was more than twice as high (10.3±0.4 mmHg) as in NCR (4.6±0.3 mmHg). There was no difference in the intrapleural pressure between the two groups of rats, therefore the enhanced left atrial pressure in SHR represents a real rise in the diastolic filling pressure of its left ventricle. This is considered to be the most important compensation for the earlier reported rightward shift of the Frank-Starling curve in SHR (Hallbäck, Isaksson & Noresson 1975, Noresson et al. 1979a). Without this compensation the stroke volume would have been drastically reduced for the hypertrophied heart.     

Renal dopamine and noradrenaline excretion during CNS‐induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS‐induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS‐induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS‐induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS‐induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS‐induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

Renal nerve activity and exaggerated natriuresis in conscious spontaneously hypertensive rats

Exaggerated natriuresis upon volume loading occurs in both human and animal hypertension and is mainly due to suppressed tubular reabsorption. To explore whether altered renal sympathetic activity contributes to this response, conscious male spontaneously hypertensive rats (SHR) were exposed to isotonic saline loading in comparison with normotensive male Wistar Kyoto rats (WKR). After a 60 min control hydropenic period, during which mean arterial pressure, heart rate, renal sympathetic nerve activity and urinary sodium excretion were followed, a 60 min period of intravenous volume expansion with isotonic saline (0.2 ml/minx 100 g b. w.) was started followed by a 60 min hydropenic recovery period. Already during the control period sodium excretion was significantly higher in SHR. During the volume load and subsequent recovery period a clearly exaggerated natriuresis occurred in SHR compared with WKR. Further, volume loading reduced renal sympathetic nerve activity in all animals, but significantly more in SHR. Moreover, volume loading reduced mean arterial pressure and heart rate in both groups. It is suggested that the accentuated reflex inhibition of renal sympathetic activity in SHR upon volume loading emanates from cardiac mechanoreceptors and partly explains the exaggerated natriuresis in SHR. This augmented ‘volume’ reflex response is probably due to reduced systemic venous compliance in SHR with a consequently increased central filling and cardiac receptor activation.     

Blood pressure and heart rate responses to mental stress in spontaneously hypertensive (SHR) and normotensive (WKY) rats on various sodium diets

Normotensive (WKY) and hypertensive rats (SHR) were, from 5 to 12 weeks of age, given ‘low’ (LNa), ‘control’ and ‘high’ (HNa) Na diets (0.5, 5 and 50 mmol-100 g^-1 food, respectively, during weekly recordings of body weight, conscious indirect systolic blood pressure (SBP) and heart rate (HR). During the last week, mean arterial pressure (MAP) and HR responses to standardized stress stimuli (air jet) were recorded before and after sequential cardiac nerve blockade. While resting, SBP was about equal in all WKY groups, but it was significantly reduced in SHR-LNa (152 mmHg versus 174 and 178 mmHg in SHR controls and HNa; P < 0.05). In both LNa groups HR was elevated nearly 25% compared with controls, being in SHR 513 versus 419 bpm (P < 0.01) and in WKY 489 versus 393 bpm (P < 0.01). Cardiac nerve blockade indicated that this HR elevation was about equally due to elevations of sympathetic activity and ‘intrinsic’ pacemaker activity. SHR-LNa also showed attenuated MAP elevations to acute mental stress. There were, however, no significant differences between groups concerning haematocrit or plasma Na-K levels. The results suggest that SHR have a greater salt requirement than WKY, as Na restriction to one-tenth of normal led to a considerable MAP reduction in SHR despite compensatory sympathetic activation, and also to attenuated pressor responses to mental stress. Further, the cardiovascular effects in SHR were much more extensive when on a low-Na diet than when Na intake was increased tenfold above normal.     

The intestinal tract and the pathophysiology of arterial hypertension: an experimental study on Dahl rats

Salt depleted rabbits and humans excrete an oral sodium load more quickly via the kidneys than an intravenous one. This has been ascribed to the presence of a sodium sensor in the gastrointestinal tract which in some way can influence renal function. The purpose of this study was to investigate this response in the Dahl rats. Renal and faecal sodium excretion was followed in the two strains of rats (normotensive, saltresistant (SR/Jr) and hypertensive, saltsensitive (SS/Jr) rats). After 4 days on a low salt diet they were given NaCl(l.5 mmol kg^-1 body wt) either by gavage or intravenously. SR/Jr rats showed an increased renal sodium excretion both after oral and intravenous sodium repletion. The excretion was 2–3 times greater after the oral than after the intravenous administration. The SS/Jr rats augmented their renal sodium excretion only after the oral load, although the sodium excretion was significantly less than in SR/Jr rats. In fact, during the first 8 h after giving sodium orally the renal excretion of sodium was on an average eight times larger in the SR/Jr than in the SS/Jr rats. Renal excretion of sodium was similar in the two strains after intravenous administration. We conclude that the hypertensive SS/Jr rats have great difficulties in excreting an oral sodium load, a phenomenon that may be of importance in the pathophysiology of arterial hypertension in this strain of rats.     

Acquisition of conditioned suppression and responsivity to thermal stimulation in spontaneously hypertensive,renal hypertensive and normotensive rats

The acquisition of conditioned suppression of instrumental responding and responsivity to thermal stimulation were assessed in spontaneously hypertensive rats of the Okamoto-Aoki strain (SHRs), renal hypertensive rats of the Wistar-Kyoto strain (WKYs), and normotensive WKY rats. Spontaneously hypertensive rats showed significantly faster acquisition of conditioned suppression than age-matched WKY normotensive rats. This acquisition difference between SHRs and normotensive WKYs was maintained even following chronic preexposure to shock alone; a treatment that retarded normal acquisition of conditioned suppression. In contrast, renal hypertensive WKYs acquired conditioned suppression at the same rate as age-matched normotensive WKYs. Spontaneously hypertensive rats and renal hypertensive WKYs both showed significantly longer latencies than normotensive WKYs to respond to thermal stimulation using a hot-plate assay. These outcomes suggest that the relationship between blood pressure and the acquisition of conditioned suppression in SHRs is either pleiotrophic or a consequence of random fixation, and that acquisition of conditioned suppression may serve as a valuable marker variable of hypertension in the SHR. The dissociation between acquisition of conditioned suppression and responsivity to thermal stimulation suggests that different mechanisms may mediate nociceptive responses to shock and thermal stimulation in these models of hypertension.     

Distensibility of left atrium in normotensive and spontaneously hypertensive rats

In spontaneously hypertensive rats (SHR) left atrial mechanoreceptors are reset. Thus, left atrial pressure must be almost twice as high in SHR as in normotensive rats to produce comparable degrees of receptor activation and reflex sympathetic inhibition. The present study was performed to investigate whether this resetting is due to a decreased atrial distensibility in SHR. Static load-length relationships were therefore investigated on isolated left atrial strips from 11 pairs of male SHR and Wistar Kyoto rats (WKR). After each experiment the strips were fixed at a passive tension of 4 mN and the average wall thickness was determined histologically. Furthermore, pressure-volume relationships were studied on non-beating, isolated left atria from SHR and WKR. Distensibility was here defined as % volume increase when LAP was increased from 2.5 to 12.5 mmHg either rapidly (0.5–1 s, “dynamic” distension) or slowly (3 min, “static” distension). Atrial wall thickness did not differ significantly in SHR and WKR. but the passive force (mN) per crossectional area exerted during elongation above 80% was greater (P<0.05) in SHR. Also the “dynamic”, but not the “static” volume distensibility was significantly lower in SHR (P<0.01). The decreased dynamic distensibility of SHR left atrial walls can at least partly explain the resetting of the atrial receptors activated during the rapid filling phase.     

Abnormal relationship between sodium excretion and hypertension in spontaneously hypertensive rats

Summary Inulin clearance, single nephron glomerular filtration rate (SNGFR), Na and K excretion were studied following an acute saline infusion in spontaneously hypertensive (Okamoto strain) rats (SH). 1. Hypertonic saline load: experiments were performed in adult and young SH rats. As compared to control normotensive Wistar rats (NT), the sodium excretion rose much less following the load in SH. During the 75 min following the beginning of the load, adult SH excreted 15% (NT: 58%) and young SH 9% (NT=38%) of the sodium load (P<0.01 in both cases). Cin were similar in SH and NT during control period, and a similar increase was observed following the load. The superficial to juxtamedullary SNGFR ratio was 0.80±0.05 in 5 non diuretic adult SH, a value not different from that found in normal rats, and 0.87±0.07 in 3 salt loaded SH, indicating that no significant intrarenal GFR redistribution occurs in SH following an acute hypertonic saline load. 2. Following an isotonic saline load, the results were not different: the percentage of the sodium load excreted was 44±5% and 10±2% in NT and SH adult rats respectively.The possibility that the observed defect in sodium excretion of SH rats involves distal tubular function is suggested by the pattern of evolution in Na and K excretion.This work was partially presented at the Symposium on Current problems of Hypertension, 1973, Mainz (Germany).Maître de Recherches INSERM.     

Dopamine receptor blockade and synthesis inhibition during exaggerated natriuresis in spontaneously hypertensive rats

Hansell , P. & Sjöquist , M. 1992. Dopamine receptor blockade and synthesis inhibition during exaggerated natriuresis in spontaneously hypertensive rats. Acta Physiol Scand 144 , 269–276. Received 21 September 1990, accepted 11 October 1991. ISSN 0001–6772. Department of Physiology and Medical Biophysics, Biomedical Centre, University of Uppsala, Sweden. The influence of dopamine receptor blockade and synthesis inhibition on natriuresis induced by isotonic saline volume expansion was investigated in anaesthetized spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The aim of the study was to elucidate the mechanisms underlying the phenomenon of exaggerated natriuresis during volume expansion that has been observed in spontaneously hypertensive rats. Volume expansion, at 5 % of body weight, resulted in a larger and faster natriuretic response in spontaneously hypertensive rats than in Wistar-Kyoto rats. Sixty minutes after commencement of volume expansion the natriuretic response (accumulated sodium excretion) in Wistar-Kyoto rats (n = 8) was only 24% of that in spontaneously hypertensive rats (n = 17). When spontaneously hypertensive rats were pretreated with the dopamine receptor blockers haloperidol (n= 14, 1 mg kg^-1), SCH23390 (n = 8, 30 μg h^-1 kg^-1) or the dopamine synthesis inhibitor benserazide (n = 8, 50 mg kg^-1; n = 5, 100 mg kg^-1), the natriuretic response to volume expansion was only 16, 35, 59 and 42%, respectively, of that in untreated SHR. The corresponding proportion in the haloperidol-treated (n= 8) compared with untreated Wistar-Kyoto rats was 22%. In conclusion, isotonic volume loading results in more pronounced natriuresis in spontaneously hypertensive than in Wistar-Kyoto rats. Dopamine receptor blockade and synthesis inhibition attenuate the expansion of exaggerated natriuresis in spontaneously hypertensive rats and reduces the volume expansion natriuresis in Wistar-Kyoto rats, indicating that the dopamine system plays an important role.     

Renal dopamine and noradrenaline excretion during CNS-induced natriuresis in spontaneously hypertensive rats: influence of dietary sodium

Abnormalities in dopamine (DA) and noradrenaline (NA) activities and sodium handling may be involved in the pathogenesis of hypertension. The present study was designed to investigate whether any differences exist between normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in urinary excretion of DA, NA and sodium after 15 weeks on a low, medium or high sodium diet and during a subsequent elevation of the cerebroventricular fluid sodium concentration (CNS-induced natriuresis). Seven features were noted: (1) Basal sodium and DA excretion after the diet regimen was correlated to the dietary sodium content in both strains, except that sodium and DA excretion in SHR showed no further increase after the high sodium diet over and above that after medium sodium diet. (2) For any given sodium diet, SHR excreted more DA and NA as compared with WKY. (3) Blood pressure in SHR, as opposed to that in WKY, was higher after medium and high sodium diet than after low sodium diet. (4) During CNS-induced natriuresis NA excretion decreased or remained unchanged in WKY, but increased in SHR. (5) The DA/NA excretion ratio during CNS-induced natriuresis increased in WKY while decreased in SHR, which would not favour a natriuretic/vasodilatory response in the latter. (6) The ability of SHR to respond with CNS-induced natriuresis was attenuated after high sodium diet. (7) The magnitude of CNS-induced natriuresis was in both strains correlated to the sodium diet; the higher the dietary sodium content, the greater the natriuretic response. In conclusion, the study shows some clear differences in the catecholamine and sodium handling between WKY and SHR which may be involved in the pathogenesis of hypertension in SHR. Furthermore, increased sodium in the diet sensitizes the brain and kidney to increase the ability to respond with natriuresis for a given sodium stimulus.     

Effect of carbocyclin on cardiac ATP-ase activity in normotensive and stroke-prone spontaneously hypertensive rats

Laboratory of Pathophysiology, Research Institute of Pediatrics, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. Ya. Studenikin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 109, No. 3, pp. 229–231, March, 1990.     

Stress ulcer in normotensive and spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and their normotensive progenitors, the Wistar-Kyoto (WKY) rats, were tested in the open-field arena and subsequently exposed to either cold-restraint stress or activity-stress. SHR rats were more active and judged less fearful in the open-field test. Changes in core body temperature, and adrenal and thymus weights did not differentiate between SHR and WKY rats in the cold-restraint procedure. A significant adrenal hypertrophy was observed for SHR rats in the activity-stress procedure. WKY rats were more susceptible to stress ulcer in both the cold-restraint and the activity-stress procedures. While running-wheel activity had been considered an important etiological variable for activity-stress ulcer, the lower activity demonstrated by the ulcer-prone WKY rats suggested that genetic variables might be more relevant to stress ulcer disease.     

Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats

The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to ‘mental stress’ in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during ‘rest’ and during a 20 min period of ‘mental stress’. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64±5%) than in WKY (-34±7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during ‘mental stress’ the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e. g. the renal and splanchnic regions during increased alertness.     

The effects of enalapril on the natriuretic response evoked by an oral sodium load in sodium deprived normotensive and hypertensive rats

Previous studies have shown that an oral sodium load during sodium deprivation is excreted faster than an intravenous load. We wanted to study whether the renin-angiotensin-aldosterone system might be associated with this phenomenon and therefore the influence of the angiotensin converting enzyme (ACE) inhibitor enalapril was investigated. The experiments were performed on four strains of rat: spontaneously hypertensive rats (SHR), Wistar-Kyoto (WKY) rats, inbred hypertension-prone (SS/Jr) and hypertension-resistant (SR/Jr) Dahl rats. In SHR and WKY rats pretreated with enalapril it was observed that an intravenous sodium load induced a renal sodium excretion which was between two and five times larger than that seen after an oral load. In SR/Jr and SS/Jr rats the sodium excretion was the same regardless of the route of administration. In SS/Jr rats sodium excretion increased three- to fourfold upon sodium repletion, whereas no significant increase was observed in SR/Jr rats. Thus, the present results indicate that an intact renin-angiotensin system is necessary for the interplay between the gastrointestinal tract and kidney.     

The early ontogeny of sodium appetite in spontaneously hypertensive vs. normotensive rats

Rats of various strains differ widely in their appetite for sodium. For example, the Okamoto-Aoki spontaneously hypertensive rat (SHR) exhibits a much greater salt appetite than its normotensive control strains. Developmental observations of salt appetite in this strain have been collected only for rats at or above weanling age. In this experiment, the salt appetite of the SHR was compared with that of normotensive Sprague-Dawley and Wistar-Kyoto rats, at 3, 6 and 12 days after birth. The results show that the increased salt appetite of the SHR is a fundamental behavioral trait that appears very early in life. This observation is consistent with a defective central angiotensin system in SHR rats.     

Increased oxytocinergic system activity in the cardiac muscle in spontaneously hypertensive SHR rats

IntroductionThe present study aimed to determine whether the presence of cardiac hypertrophy due to arterial hypertension is associated with a change in the activity of the oxytocinergic system in cardiomyocytes.Material and methodsThe experiments were performed on male, spontaneously hypertensive rats (SHR, n = 10) and normotensive Wistar-Kyoto rats (WKY, n = 12). Blood samples were collected from both SHR and WKY animals to asses plasma oxytocin (OT) concentration; the rats were sacrificed by decapitation. Samples of the left and right ventricles were harvested for the analysis of the OT and oxytocin receptor (OTR) protein by ELISA, and OT and OTR mRNA expression by RT-PCR. Immunohistopathological studies were performed to confirm the presence of OTR receptors in the cardiac muscle of the ventricles.ResultsPlasma OT concentration did not differ between SHR and WKY rats. In the SHR rats, the expression of OT mRNA and the OT protein level was higher in the left and the right ventricle, while OTR mRNA expression was significantly lower in both the left and the right ventricle. However, the level of OTR protein was higher only in the left ventricle of the SHR rats. The presence of OTR receptors was confirmed by immunohistochemical analysis in the muscle of the right and left ventricle.ConclusionsThe presence of arterial hypertension is associated with increased activity of the oxytocinergic system in the heart, especially in the area of the left ventricle. These findings support the important role of this system in the maintenance of cardiovascular homeostasis.     

The distribution of sodium in aortic walls from spontaneously hypertensive and normotensive rats.

The contents of exchangeable sodium, bound sodium and total water and the extracellular space of thoracic aortas from normotensive and spontaneously hypertensive rats were measured. The aortas from the hypertensive rats contained more sodium than those from the normotensive animals while the total water content and extracellular space in the two groups were the same. The capacity to bind sodium in an osmotically inactive form was greater in the aortas from the hypertensives than in those from the normotensives. The difference in binding capacity was of the same order of magnitude as the difference in sodium content, indicating that the excess sodium in the thoracic aortas from the hypertensive rats was osmotically inactive and thus unable to cause water logging.