Brainstem oxytocinergic modulation of heart rate control in rats: effects of hypertension and exercise training

Oxytocinergic brainstem projections participate in the autonomic control of the circulation. We investigated the effects of hypertension and training on cardiovascular parameters after oxytocin (OT) receptor blockade within the nucleus tractus solitarii (NTS) and NTS OT and OT receptor expression. Male spontaneously hypertensive rats (SHR) and Wistar–Kyoto (WKY) rats were trained (55% of maximal exercise capacity) or kept sedentary for 3 months and chronically instrumented (NTS and arterial cannulae). Mean arterial blood pressure (MAP) and heart rate (HR) were measured at rest and during an acute bout of exercise after NTS pretreatment with vehicle or OT antagonist (20 pmol of OT antagonist (200 nl of vehicle)^–1). Oxytocin and OT receptor were quantified (³⁵S-oligonucleotide probes, in situ hybridization) in other groups of rats. The SHR exhibited high MAP and HR ( P < 0.05). Exercise training improved treadmill performance and reduced basal HR (on average −11%) in both groups, but did not change basal MAP. Blockade of NTS OT receptor increased exercise tachycardia only in trained groups, with a larger effect on trained WKY rats (+31 ± 9 versus +12 ± 3 beats min⁻¹ in the trained SHR). Hypertension specifically reduced NTS OT receptor mRNA density (–46% versus sedentary WKY rats, P < 0.05); training did not change OT receptor density, but significantly increased OT mRNA expression (+2.5-fold in trained WKY rats and +15% in trained SHR). Concurrent hypertension- and training-induced plastic (peptide/receptor changes) and functional adjustments (HR changes) of oxytocinergic control support both the elevated basal HR in the SHR group and the slowing of the heart rate (rest and exercise) observed in trained WKY rats and SHR.     

Arteriolar closure mediated by hyperresponsiveness to norepinephrine in hypertensive rats.

This study was designed to determine if a mechanism exists to cause abnormally large number of arterioles to be closed to blood flow in spontaneously hypertensive rats (SHR). The contributions to vessel closure by neural control and constrictor response to norepinephrine were investigated. Normal rats (WKY) and SHR were studied at age 18--20 wk. Their respective mean arterial blood pressures were 100 +/- 4 (SE) and 154 +/- 7 mmHg when anesthetized with 10% urethan and 2% alpha-chloralose (0.6 mg/100 g ip). The number of arterioles open to blood flow was counted in a large portion of the cremasteric muscle before and after denervation. The percent change in control diameter of denervated arterioles was measured during iontophoretic application (2 min) of norepinephrine at dose currents of 10--300 nA. Following denervation, a 22.2 +/- 6.3% (SE) and 61.8 +/- 12 increase in the number of third-order arterioles open to flow occurred in WKY and SHR. The diameters, wall thicknesses, and cross-sectional areas of vessel walls were not significantly (P less than 0.05) different for comparable types of denervated arterioles in WKY and SHR. The percent changes in diameters of arterioles in SHR were 3--5 times greater at all dose currents than for vessels of WKY. These data indicate arteriolar closure occurs with higher incidence in SHR than WKY and is mediated by hyperresponsiveness of arterioles to norepinephrine.     

Microanatomical changes of intracerebral arteries in spontaneously hypertensive rats: a model of cerebrovascular disease of the elderly.

Changes occurring in intracerebral arteries of 24-week-old spontaneously hypertensive rats (SHR) compared with age-matched normotensive Wistar-Kyoto (WKY) rats were assessed using microanatomical techniques associated with image analysis. Morphometric parameters investigated included arterial diameter, lumen area, wall area, and wall-to-lumen ratio. Intracerebral arteries (lumen diameter>46 microm) and arterioles (lumen diameter 46-10 microm) of frontal cortex, striatum, and hippocampus were examined. In frontal cortex of SHR arterial wall hypertrophy and luminal narrowing were observed. In striatum, an increase of wall area not accompanied by luminal narrowing predominates resulting in arterial hypertrophy without vasoconstriction. In hippocampal arteries of SHR, luminal narrowing, without changes of wall area was found indicating the occurrence of remodeling. In brain areas investigated, hypertensive changes affected primarily arterioles. The demonstration of a sensitivity of intracerebral arteries to hypertension suggests that changes of these vessels may represent a cause of brain structural alterations occurring in hypertension. The specificity of alterations occurring in intracerebral arteries of brain areas investigated may account for the different localization of cerebral lesions in cerebrovascular disease. The possibility that microanatomical changes developed in intracerebral arteries of SHR may represent a model of cerebrovascular disease of the elderly is discussed.     

Spontaneous variations in arterial blood pressure, heart rate and sympathetic nerve activity in conscious normotensive and spontaneously hypertensive rats

In the present study we have recorded spontaneous variations in mean arterial blood pressure (MAP), heart rate (HR) and mean rectified splanchnic nerve activity (SNA) in conscious undisturbed normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The variability in blood pressure was not significantly different but HR variability tended to be lower in SHR. The variability in SNA expressed as % change from mean value was not significantly different between SHR and WKY. By computer techniques the correlation between HR, MAP and SNA could be calculated during spontaneous variations of these parameters. The slope of the regression line correlating HR and SNA was significantly steeper in SHR than in WKY (0.73, 0.47 resp.). Thus a certain change in HR was associated by a greater change in SNA in SHR compared with WKY. Spontaneous changes in SNA could be divided in principally two different patterns. One typical pattern was a rise in SNA in parallel with a drop in MAP. This pattern was most likely triggered by the arterial baroreceptors and was called a "baroreceptor-pattern". Marked spontaneous excitations in SNA and HR was also observed during natural behaviours such as eating, drinking and explorative behaviour, a so called "centrally mediated pattern".     

Stimulation of arteriolar number by salbutamol in spontaneously hypertensive rats.

Experiments were performed to study beta2-adrenergic involvement in arteriolar development in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. Newly weaned 20-day WKY and SHR rats were injected with salbutamol, a selective beta2-agonist (50 microgram/day sc, plus 5 mg/100 ml in drinking water), for 20 days. At 40 days, under 2% chloralose-7.5% urethan anesthesia (6 ml/kg), either the cremaster muscle was prepared for in vivo microscopy to estimate the number and diameter of open arterioles or the arterioles were injected with latex to determine the total number of arterioles and their maximal diameters. Control SHRs had 62% (P less than 0.01) fewer open arterioles and a 32% (P less than 0.001) reduction in the total number of arterioles compared to WKY controls. Salbutamol stimulated 67% (P less than 0.001) and 22% (P less than 0.05) increases in total number of the smallest arterioles in the SHR and the WKY, respectively. Salbutamol also significantly reduced the maximum diameter of latex-injected arterioles. These results suggest that the decreased arteriolar density in the cremaster muscle of SHR rats may result from differences in the beta-adrenergic mechanism.     

Cardiac design and pressure-volume characteristics of the left ventricle in normotensive (WKY) and hypertensive (SHR) rats after various dietary sodium treatments

Normotensive (WKY) and hypertensive rats (SHR) from 5 to 13-14 weeks of age were given 'low' (LNa; 0.5 mmol Na 100 g-1 food), 'control' (CNa; 5 or 12 mmol), 'high' (HNa; 50 mmol) and in SHR also 'medium low' (mLNa; 2 mmol) and 'very high' (vHNa; 120 mmol) sodium diets, to explore how such 240-fold variations in Na intake affect cardiac design. This was assessed in isolated perfused, temporarily-arrested hearts by recordings of left ventricular (LV) diastolic pressure-volume relationships (P/V), LV and RV weights, and by calculations of the ratio between LV wall thickness and internal radius (w/ri), after in vivo recordings of awake mean arterial pressure (MAP) and heart rate (HR). In WKY, where MAP was the same in all diet groups, the HNa group showed an increased w/ri due to a 20% reduction of LV diastolic volume, with signs of reduced wall compliance compared with CNa. The LNa WKY showed less marked changes in the same direction. In the SHR LNa group, where MAP was lowered about 20 mmHg, LV diastolic volume was reduced nearly 20% at a modest w/ri increase, while HNa and Cna SHR had equal MAP, LV weights, P/V and w/ri relationships. However, in vHNa SHR, where MAP was elevated about 25 mmHg, the LV showed a mainly eccentric hypertrophy with 15% increase of diastolic volume at a slight increase of w/ri. These differentiated, and in WKY and SHR partially differing structural cardiac adaptations consequent to changes in Na intake, can hardly be ascribed only to the respective pre- and afterload alterations, suggesting that also altered neuro-hormonal profiles may have contributed with 'trophic' influences.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction between "mental stress" and baroreceptor reflexes concerning effects on heart rate, mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared concerning the interactions between cortico-hypothalamic alerting responses and baroreflex influences on neurogenic cardiovascular control. For this purpose mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were continuously recorded during night time in conscious, otherwise undisturbed rats. Baroreceptor sensitivity was assessed as percentage HR and RSNA reductions per mmHg MAP elevation when a standardized phenylephrine infusion was performed. A state of acute "mental stress" could be induced by a likewise standardized sudden blowing of air. These two opposing influences on neurogenic cardiovascular control were also experimentally superimposed in various ways and the effects on MAP, HR and RSNA followed. During "rest" RSNA was higher in SHR than in WKY and it also increased more during "mental stress". The baroreflex sensitivity was clearly reduced in SHR and WKY concerning HR reduction (0.44 +/- 0.06 vs. 0.78 +/- 0.08%/mmHg; p less than 0.01) but not so concerning RSNA, which was similar in SHR and WKY (2.6 +/- 0.2 vs. 2.9 +/- 0.4%/mmHg). If expressed (HR + 1 +/- 3%; p less than 0.025 vs. SHR and RSNA + 11% +/- 10, p less than 0.01 vs. SHR). These results) (0.10 +/- 0.02 vs. 0.06 +/- 0.01 microV/mmHg; p less than 0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction between “mental stress” and baroreceptor reflexes concerning effects on heart rate,mean arterial pressure and renal sympathetic activity in conscious spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) were compared concerning the interactions between cortico-hypothalamic alerting responses and baroreflex influences on neurogenic cardiovascular control. For this purpose mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were continuously recorded during night time in conscious, otherwise undisturbed rats. Baroreceptor sensitivity was assessed as percentage HR and RSNA reductions per mmHg MAP elevation when a standardized phenylephrine infusion was performed. A state of acute “mental stress” could be induced by a likewise standardized sudden blowing of air. These two opposing influences on neurogenic cardiovascular control were also experimentally superimposed in various ways and the effects on MAP, HR and RSNA followed. During “rest” RSNA was higher in SHR than in WKY and it also increased more during “mental stress”. The baroreflex sensitivity was clearly reduced in SHR and WKY concerning HR reduction (0.44±0.06 vs. 0.78±0.08%/mmHg; p<0.01) but not so concerning RSNA, which was similar in SHR and WKY (2.6±0.2 vs. 2.9±0.4%/mmHg). If expressed (HR + 1±3%; p<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results) (0.10±0.02 vs. 0.06±0.01 μV/mmHg; p<0.12). Also single fibre recordings in anaesthetized rats showed the same principle difference between SHR and WKY. Addition of “mental stress” during phenylephrine baroreflex activation clearly increased both HR (24±7%) and RSNA (114±21 %) in SHR, while almost no change then occurred in WKY (HR + 1±3%; p<0.025 vs. SHR and RSNA + 11%±10, p<0.01 vs. SHR). These results suggest that a modestly accentuated cortico-hypothalamic activity ordinarily prevails in SHR, explaining the suppressed baroreflex control of heart rate and the augmented sympathetic activity to e.g. renal and splanchnic areas. Further, environmental alerting stimuli induce in SHR more powerful defence reactions which, unlike the situation in WKY, readily overcome baroreflex inhibitory influences on sympathetic activity.     

Blood pressure and heart rate responses to mental stress in spontaneously hypertensive (SHB) 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 X 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 less than 0.05). In both LNa groups HR was elevated nearly 25% compared with controls, being in SHR 513 versus 419 bpm (P less than 0.01) and in WKY 489 versus 393 bpm (P less than 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.     

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.     

Variations in arterioles in spontaneously hypertensive rats

Summary In the present study, the diameters of afferent and efferent arterioles of kidneys from spontaneously hypertensive rats (SHR) were evaluated and compared with those from Wistar Kyoto rats (WKY) using a vascular cast model. At 4 weeks of age, the blood pressure was slightly higher in SHR than in WKY (124±1 vs 116±7 mmHg, ns). The diameters of afferent arterioles in SHR were smaller than those in WKY (10.3±0.6 vs 12.3±0.7 µm,P<0.001), whereas the diameters of efferent arterioles were comparable in the two strains. At 20 weeks of age, the blood pressure was markedly elevated in SHR than in WKY (192±5 vs 140±4 mmHg,P<0.001). The diameters of afferent arterioles in SHR at this age were much smaller than those in WKY (14.3±0.5 vs 17.1±0.6 µm,P<0.01). The diameters of efferent arterioles in SHR were, however, larger than those in WKY (15.4±l.2 vs 12.9±0.4 µm,P< 0.05). The net effect of these changes in arteriolar size helps to maintain normal intraglomerular pressure and to protect glomeruli from damage due to hypertension.     

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.     

Sodium appetite as well as 24-h variations of fluid balance, mean arterial pressure and heart rate in spontaneously hypertensive (SHR) and normotensive (WKY) rats, when on various sodium diets

Young SHR and WKY rats were compared, first, concerning sodium (Na) appetite during 'rest', mild social stress and ACTH injections, second, concerning the diurnal patterns of water intake, urine output, mean arterial pressure (MAP) and heart rate (HR) while on various Na diets: 0.5 mmol Na(LNa), 5 or 12-13 mmol Na (CNa), 50 (HNa) or 120 mmol Na (vHNa) per 100 g food. Sodium appetite and water intake were about 50% higher in SHR than in WKY (4-4.5 vs 2.5-3 mmol Na per 100 g body wt day-1). It was modestly increased by both social stress and ACTH, and more so in WKY, thereby approaching that in SHR. Concerning the various Na diets and their influences, daytime resting MAP was modestly lowered in LNaSHR and slightly increased in vHNaSHR compared with CNaSHR but largely equal in all WKY groups. Food-water consumption was concentrated to the active night period, but even high Na-water intakes caused no signs of sustained hypervolaemia, because each intake bout was in both SHR and WKY eliminated by urine within 30-40 min. However, particularly the vHNa diet in SHR also increased the frequency of drinking, and each bout caused transient, evidently neurogenic MAP and HR increases which occurred too rapidly to be consequences of blood volume expansion. As a result, the diurnal MAP-HR patterns in SHR varied markedly with the Na diets, in vHNa group resulting in considerably raised average diurnal MAP levels even though resting daytime MAP was here nearly the same as in CNaSHR. These findings illustrate how largely continuous diurnal recordings are needed to judge correctly the relationships between, for example, Na intake, volume equilibrium and MAP. Finally, the relevance of these results in rats for also judging the control of Na balance in man is discussed.     

自发性高血压大鼠多器官微血管稀少动态观察

本研究旨在对自发性高血压大鼠多器管微血管稀少作动态观察。研究对象为自发性高血压大鼠组:5周龄、8周龄、13周龄。WKY组:5周龄、8周龄,13周龄。观察参数为小动脉A_2、A_3、A_4。研究结果显示:(1)自发性高血压鼠视网膜A_2、A_3、A_4进行性减少。(2)自发性高血压鼠心、肾、肌肉小动脉面积密度进行性减少。提示自发性高血压大鼠存在多器管微血管稀少。     

Connexin abundance in resistance vessels from the renal microcirculation in normo‐ and hypertensive rats

The expression of connexins in renal arterioles is believed to have a profound impact on conducted responses, regulation of arteriolar tonus and renal blood flow. We have previously shown that in renal preglomerular arterioles, conducted vasomotor responses are 40% greater in spontaneously hypertensive rats (SHR) than in normotensive Sprague–Dawley (SD) rats. Because conducted vasomotor responses depend on the cell–cell communication mediated through gap junctions, we hypothesized that the increased magnitude of conducted vasomotor response in SHR is associated with an increased amount of connexins in renal arterioles. To test this hypothesis, the amount of connexin 37 (Cx37), Cx40 and Cx43 was assessed in renal arterioles from normo‐ and hypertensive rats using quantitative immunofluorescence laser confocal miscroscopy. To account for differences in genetic background, we included both normotensive Wistar–Kyoto (WKY) and SD rats in the study. In all three strains of rats, and for all three isoforms, the expression of connexins was predominantly confined to the endothelial cells. We found a significantly increased abundance (240 ± 17.6%, p<0.05) of Cx37 in arterioles from WKY compared with SD and SHR. This high abundance of Cx37 was not related to blood pressure because normotensive SD demonstrated a level of Cx37 similar to that of SHR. Additionally, we found no evidence for an increased abundance of Cx40 and Cx43 in renal arterioles of SHR when compared with normotensive counterparts.     

Elevated arteriolar adenosine 3',5'-cyclic monophosphate production by SHR

Adenosine 3',5'-cyclic monophosphate (cAMP) metabolism was studied in the microcirculation (100- to 150-micrometers arterioles) of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at different stages of hypertension. Mesenteric arterioles from animals 4, 6, 12, and 18 wk old were incubated in Krebs-Ringer bicarbonate buffer for 30 min at 37 degrees C, pH 7.4, with and without the phosphodiesterase inhibitor, 1-methyl-3-isobutylxanthine (MIX). cAMP was assayed by radioimmunoassay. Arteriolar production of cAMP was age related in both WKY and SHR rats although the temporal patterns were different. At 6 wk (developmental stage of hypertension in SHR) cAMP accumulation in the presence or absence of MIX by SHR arterioles was higher than in the WKY before falling to normotensive levels at 12 wk. Salbutamol (a beta 2-agonist) stimulated dose-dependent increases in cAMP in both WKY and SHR at 6 wk. Stimulation of cAMP by salbutamol or by isoproterenol was blocked by propranolol. Neither agonist increased guanosine 3',5'-cyclic monophosphate. These data indicate that differences in cAMP metabolism are evident at the arteriolar level during the developmental stage of SHR hypertension. These differences may contribute to the morphological and physiological changes occurring at this time.     

Structural adaptation of the rat left ventricle in response to changes in pressure and volume loads

Female Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were used to explore the structural changes of cardiac dimensions in connection with a sustained hyperkinetic circulation, as induced by pregnancy or thyroxine administration. Cardiac design was assessed by recordings of the diastolic left ventricular pressure-volume relationships in isolated arrested hearts. Left ventricular weight: body weight and end-diastolic volume (EDV) for given end-diastolic pressures (EDP), were both increased about 50% in control SHR, with a marginal reduction of the wall:lumen ratio (w:ri) compared with control WKY. During the hyperkinetic circulatory states of pregnancy and hyperthyroidism, EDV was in WKY increased about 30% and 50%, respectively, with concomitant w:ri reductions. In SHR pregnancy did not significantly alter left ventricular dimensions, whereas EDV was increased by about 20% in hyperthyroid SHR. Thus, the rat left ventricle can, within 3 weeks, markedly alter not only the wall mass but also, and independently, the luminal design in response to different haemodynamic interventions. Early established SHR hypertension is characterized mainly by eccentric left ventricular hypertrophy, despite the elevated arterial pressure. Volume overloads in WKY due to pregnancy or hyperthyroidism can induce marked structural widening of the left ventricle. In SHR these structural luminal changes were only minor, perhaps because considerable eccentric hypertrophy is already present. Such a structural cardiac enlargement may allow delivery of an increased stroke volume for a given myocardial fibre shortening.     

The effect of renal perfusion pressure on renal vascular resistance in the spontaneously hypertensive rat

Renal hemodynamics and renal vascular resistance (RVR) were measured in the spontaneously hypertensive rat (SHR) and in the normotensive Wistar-Kyoto rat (WKY). In addition, the autoregulatory response and segmental RVR in the SHR were studied after aortic constriction. Mean arterial pressure (MAP) and RVR were higher in the SHR than in the WKY, but renal blood flow (RBF) and glomerular filtration rate were similar in both groups. Measurement of mean afferent arteriolar diameter (AAD) by a microsphere method showed a significantly smaller AAD in SHR (17.7±0.35 m) than in the WKY (19.5±0.20 m). This decrease in AAD could account for a 47% increase in preglomerular resistance. Aortic constriction in the SHR, sufficient to reduce renal perfusion pressure from 152 to 115 mm Hg, did not alter the AAD. Since RBF and glomerular filtration were also well maintained following aortic constriction, these autoregulatory responses suggest that vessels proximal to the afferent arteriole rather than postglomerular vasculature are primarily involved in the changes on intrarenal vascular resistance in SHR.     

Cerebral function during hypotensive haemorrhage in spontaneously hypertensive rats and Wistar Kyoto rats

Studies on cerebral function during cerebral ischaemia are usually performed on conscious animals after ligation of a major vessel supplying the brain. In this work, we studied somatosensory evoked potentials (SEP) in chloralose-anaesthetized Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) during hypotensive haemorrhage, with the main emphasis on the SHR which are more vulnerable. The main purpose was to see whether haemorrhaged SHR could be used for studies of cerebral function during relative cerebral ischaemia in anaesthetized rats. The mean arterial pressure (MAP) was rapidly lowered to 45-50 mm Hg and maintained at that level by adjustments of bleeding and transfusion. This resulted in pronounced sympathetic inhibition and bradycardia in all rats. In SHR, this sympatho-inhibitory response was usually reversed after about 20 min. In one group of hypertensive rats (SHRt, n = 24), MAP was raised to 75 mm Hg by partial re-transfusion, when heart rate (HR) had returned to the pre-bleeding level and MAP was maintained at that level for the rest of the experiment. All the other rats (SHR, n = 12; WKY, n = 11) were kept at 45-50 mm Hg for 32 min, after which WKY were bled further to a MAP of 30 mm Hg for 8 min. SEP amplitudes decreased after haemorrhage in all groups but more so in SHR. In the WKY group, SEP were only modestly attenuated during the first 32 min, but after further bleeding to 30 mm Hg the amplitudes were reduced to the same extent as in SHR. Some SHR showed flat SEP immediately upon haemorrhage and were excluded from the SHRt group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulatory events following spontaneous muscle exercise in normotensive and hypertensive rats

In previous studies we have shown that spontaneously hypertensive rats (SHR) develop a running behaviour and, secondary to the running behaviour, develop an endorphin-mediated analgesic effect. In the present study the role of the central endorphin system in the cardiovascular responses to spontaneous exercise in normotensive Wistar Kyoto rats (WKY) and SHR was investigated. The experimental design allowed us to record mean arterial pressure (MAP) and heart rate (HR) continuously for more than 1 week without interfering with the daily activities of the animals. They were active in running wheels during the dark period (19.00-07.00 h) and the activity was accompanied by a marked rise in HR. In SHR, a clear depression of blood pressure lasting for about for about 50 min was noted following each running period. The MAP during the post-running depression was 131.4 +/- 1.6 mmHg which was significantly lower than the pre-running control value (145.2 +/- 2.3 mmHg, P less than 0.01). In contrast, MAP in the post-running period in WKY was not significantly different from the pre-running values. In addition, the depression period of SHR had a mean post-running length of 49.7 +/- 3.4 min, which is significantly longer than in the WKYs (37.8 +/- 3.5 min, P less than 0.05). In control rats, naloxone infusion had no effect on blood pressure but a marked bradycardia was observed. In nine running SHR receiving a naloxone infusion, their MAP during the depression period was not different from the control pressure. Our study indicates that endorphin systems are involved in the regulating of blood pressure and HR during muscle exercise in SHR. These systems trigger the transient depression of blood pressure observed immediately after a running period in the SHR.