Ontogenic Development of the Elastic Component of the Aortic wall in Spontaneously Hypertensive Rats

In the neonatal stage of development in spontaneously hypertensive rats (SHR), previous studies have shown that arterial pressure is already significantly increased over that of normotensive WKY controls and that other hypertensive characteristics of the cardiovascular system are also in evidence. The present study describes early development of the elastic component of the aortic wall in fetal (days 17,19,21–22 of gestation) and neonatal (days 1,7,14,21 of age) SHR and WKY, to determine whether the early pattern of elastin accumulation differs significantly in hypertensive and normotensive animals. The data indicate that in SHR there is a greater concentration of elastin in the aortic wall, a larger cross-sectional area and an increase in the number of lamellar units, both pre- and postnatally. We conclude that the differences in arterial wall structure which are associated with genetic hypertension are established early in development.     

Changes in Creatine Kinase Expression Induced by Exercise in Borderline Hypertensive Rat Hearts

Hypertrophy in hypertensive hearts is associated with increased risk of cardiac morbidity and mortality that is not characteristic of exercised hearts. This study was done to determine whether exercise training of normotensive and borderline hypertensive rats induces the increased myocardial expression of BB and MB isoforms of creatine kinase (CK) that characterizes hypertensive hypertrophy. Spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats were subjected to either an 8% sodium chloride diet or swim training to produce myocardial hypertrophy. Both exercise and a high salt diet induced an increase in the combined expression of CK-MB and CK-BB in SHR after 2 months. However, since swimming also exacerbated hypertension in SHR, exercise induced effects on CK were not distinguishable from those of hypertension. In WKY, neither exercise nor a high salt diet induced significant changes in CK isozyme expression. In BHR fed a high sodium chloride diet, significant increases in mean arterial pressure and left ventricular weight to body weight were not associated with changes in CK expression. In contrast, following 10 months of swim training BHR exhibited mild hypertrophy, decreased resting heart rates, and an increase in the combined expression of CK-MB and CK-BB. Therefore, exercise associated with a cardiac training effect in BHR induced changes in CK isozyme expression similar to those in hypertensive hearts.     

Insulin resistance in spontaneously hypertensive rats but not in deoxycorticosterone-salt or renal vascular hypertension.

OBJECTIVE: To investigate whether the reported association between insulin resistance and hypertension in spontaneously hypertensive rats (SHR) is a primary defect or a secondary phenomenon in hypertension. DESIGN: Comparisons of glucose metabolism between three groups of hypertensive rats: deoxycorticosterone (DOCA)-salt hypertensive rats; two-kidney, one clip renovascular hypertensive (RVH) rats; SHR; and their respective control groups. There was also an additional group of weight-matched SHR and respective Wistar-Kyoto (WKY) controls. METHODS: A trace amount of 3H-deoxyglucose (3H-DOG) was administered in vivo to evaluate its plasma half-life and tissue uptake. In vitro adipose tissue segments were incubated with 14C-glucose and increasing doses of insulin. RESULTS: Compared with age-matched WKY rats, SHR had significantly higher insulin levels, longer plasma half-life and lower 3H-DOG uptake by heart and striated muscle. Plasma glucose levels and incorporation of 14C-glucose into CO2, triglycerides and glycogen by adipose tissue in response to increasing insulin concentrations was similar for both groups of SHR and WKY rats. No differences were found between hypertensive rats and controls in either the DOCA or RVH groups. CONCLUSION: Evidence of insulin resistance in spontaneous, but not secondary, rat hypertension indicates that the resistance is a primary rather than a secondary event in hypertension.     

Diltiazem maintains renal vasodilation without hyperfiltration in hypertension: Studies in essential hypertensive man and the spontaneously hypertensive rat

Summary The systemic and renal hemodynamic effects of diltiazem were determined in patients with mild to moderately severe essential hypertension and in rats with spontaneous hypertension (SHR). Seven patients were treated for one full year (300 mg/day, average dose) and 10 SHR and 10 normotensive Wistar-Kyoto (WKY) rats received 1 and 2 mg/ kg, intravenously. In both man and rat with genetic hypertension, arterial pressure was reduced through a fall in total peripheral resistance without associated reflexive increases in heart rate and cardiac index; and the patients demonstrated no change in plasma volume. In both man and the SHR: renal blood flow increased (in SHR not statistically significant) as arterial pressure and renal vascular resistance fell; glomerular filtration rate (GFR) remained unchanged and the filtration fraction (FF) significantly fell; and calculated intrarenal hemodynamic indices (using the Gomez formulae) demonstrated falls in afferent and efferent glomerular arteriolar pressures and resistances and in intraglomerular pressures, thereby explaining the unchanged GFRs and the decline in FF. These findings in both hypertensive man and rat are in contrast with those of the normotensive WKY that only demonstrated a fall in afferent glomerular arteriolar resistance. Thus, these data demonstrate that diltiazem controlled arterial pressure in both forms of genetic hypertension associated with falls in systemic and renal arteriolar resistances and with improved intrarenal hemodynamics without glomerular hyperfiltration.     

Cerebrovascular and brain microanatomy in spontaneously hypertensive rats with streptozotocin-induced diabetes

The influence of hypertension associated with diabetes on cerebrovascular and frontal cortex or hippocampus microanatomy was investigated in 20-week-old spontaneously hypertensive rats (SHR) in which diabetes was induced by treatment with streptozotocin (STZ) and in control or STZ-diabetic age-matched normotensive Wistar Kyoto (WKY) rats. At the beginning of experiment, systolic pressure values were similar in WKY rats either control, or exposed to STZ and remarkably higher in control or STZ-treated SHR. Systolic pressure values increased in the different animal groups examined along the course of experiment. Blood glucose levels were increased in either STZ-WKY rats or -SHR compared to WKY rats and SHR respectively. The main changes occurring in pial and intracerebral arteries of SHR and STZ-SHR were thickening of the arterial wall accompanied by luminal narrowing. In medium sized pial arteries of STZ-WKY rats luminal narrowing and a decreased thickness of arterial wall were noticeable. Intracerebral arteries of STZ-WKY diabetic rats showed a not homogeneous sensitivity of different sized branches. The volume of zones III and IV of frontal cortex was decreased in SHR and STZ-SHR compared to control WKY rats. The number of nerve cells in these cerebrocortical layers was decreased to a similar extent in SHR. STZ-WKY rats or STZ-SHR compared to control WKY rats. In dentate gyrus, followed by the CA1 subfield of hippocampus, decreased volume and number of neurons were found in SHR and STZ-SHR compared to control WKY rats. The occurrence of astrogliosis was observed in hypertensive, diabetic or hypertensive plus diabetic rats. The above findings indicate the occurrence of cerebrovascular and brain microanatomical changes in SHR and to a lesser extent in STZ-diabetic rats compared to control normotensive and normoglicemic WKY rats. Association of hypertension and diabetes caused more pronounced changes than in the single disease models. These results support the view that hypertension and diabetes affect the structure of cerebrovascular tree and of brain and that association of the two diseases results in an increased risk of target-organ damage, involving brain.     

Central and Peripheral Contributions of the Renin-Angiotensin System in Two Models Experimental Hypertension in Rats

To examine the relationships between the central and pepirheral renin angiotensin system in normotensive Wistar Kyoto (WKY) rats, two-kidney, one-clip Goldblatt renovascular hypertension (RVH), spontaneously hypertensive rats (SHR), SQ 14225 (captopril) was administered intraventricularly (IVT and intravenously (IV) in the alternative manner and there combination. Also, the effects of IVT captopril on the peripheral sympathetic nervous system were evaluated using an intravenous injection of prazosin.

IVT captopril induced a significant reduction of blood pressure in both types hypertensive rats but not in normotensive rats. Greater depressor effects of IV captopril not IV prazosin following IVT captopril were observed in RVH. compared to those in SHR.

These results indicate that the pressor action of the brain renin angiotensin system is closely related with the sympathetic nervous system in hypertensive conditions and that these functions are independent from the peripheral renin angiotensin system. Furthermore. their roles were different in different types of experimental hypertension in rats.     

Hemodynamic Effects on Thrombogenesis and Platelet Aggregation in Spontaneously Hypertensive Rats

The present study was conducted to investigate the effect of hypertension on the formation of arterial thrombus in the rat femoral artery. The time required to establish the thrombus following endothelial injury in spontaneously hypertensive rats (SHR) was extremely prolonged. Pretreatment with prazosin which lowered the blood pressure near the level in normotensive Wistar Kyoto (WKY) rats, significantly shortened the thrombogenesis time, but it was still longer than that in WKY rats. Platelet aggregation in response to collagen with washed platelets and whole blood was reduced in SHR with and without hypotensive treatment, in comparison with that in WKY rats. Prazosin did not affect the platelet aggregability. Therefore, the decreased platelet aggregation was considered to be responsible for the delayed thrombus formation in hypotensively treated SHR. These results suggested that high blood pressure, mainly, interferes with the establishment of thrombus directly. Hypoaggregability of platelets is likely to be partly involved in the prolongation of thrombogenesis in SHR.     

Brainstem PNMT Neurons and Experimental Hypertension in the Rat

The number of phenylethanolamine-N-methyl transferase (PNMT) cells visualised with immunohistochemical techniques in the medulla oblongata is increased by 20% in 4 week old spontaneously hypertensive rats (SHR) and stroke prone spontaneously hypertensive rats (SHR-SP). This is associated with a 50% increase in the activity of PNMT and a significant rise in the amount of PNMT enzyme protein present in the medulla and spinal cord of both 4 weeks old and 4 months old SHR and SHR-SP.

Since previous experiments had demonstrated that sinoaortic denervation also increased spinal cord PNMT activity we subjected normotensive Wistar Kyoto control rats (WKY) and hypertensive SHR and SHR-SP to denervation and measured the changes in blood pressure and in PNMT activity. Mean arterial pressure rose immediately after denervation in all 3 strains of rats, with much greater rises in the SHR and SHR-SP than in WKY, but the increase in pressure was only sustained in the normotensive WKY, in which it remained elevated throughout the one week observation period. In a similar way, denervation of the arterial baro-receptors increased the activity of PNMT in the medulla and spinal cord of normotensive WKY controls, confirming the results of previous studies but was not able to increase the already elevated PNMT levels in the SHR and SHR-SP any further in these two tissues. We suggest that there is good evidence that PNMT neurons contribute t o the maintenance and elevation of arterial pressure in both the neurogenic and genetic models of hypertension. It also seems likely that the activity of descending spinal PNMT neurons is more important in the maintenance of a sustained increase in pressure than in the induction of a transient rise.     

On the Abnormalities of Contractile Responses of Rat Vasa Deferentia to Norepinephrine in Genetic Hypertension

Contractile responses to norepinephrine (NE) of strips of vasa deferentia from prostatic end isolated from rats with genetic hypertension and deoxycorticosterone (DOC)-salt induced hypertension were examined. Maximum responses to NE of vasa deferentia from all hypertensive and corresponding normotensive control rats were biphasic. Spontaneous rhythmic activities superimposed on the NE-induced contraction were observed in roost of the SHR (spontaneously hypertensive rat) strips, some of the WKY (Wistar-Kyoto normotensive rat) strips and none of the NWR (regular normotensive Wistar rat) strips. Neither the fast- nor the slow-component of the maximum contractile response to NE was altered in the vasa deferentia from SHR compared to those from WKY and in vasa deferentia from DOC-salt hypertensive rats (DHR) compared to those from the corresponding DOC-salt treated but normotensive controls (DNR). However, the strips from NWR developed significantly greater tension than those from WKY and DNR. Our findings suggest that interpretation of studies on hypertension in rats should take into account differences between tissues related to the strain of the rats used as controls for genetic hypertension     

Characterization of angiotensin converting enzyme in isolated cerebral microvessels from spontaneously hypertensive and normotensive rats.

OBJECTIVE: Abnormalities in the vascular renin-angiotensin system have been hypothesized to contribute to the pathogenesis and complications of hypertension. In animal models of hypertension, there is wide variation in reported vascular angiotensin converting activity, particularly in cerebral microvessels. In this study, we sought to characterize, quantitate and compare cerebral microvessel angiotensin converting enzyme (ACE) in genetically hypertensive rats and normotensive rats. DESIGN: Brain microvascular ACE from 14-week-old spontaneously hypertensive rats (SHR) was measured and compared with ACE from brain microvessels of normotensive Wistar-Kyoto (WKY) controls. METHODS: Isolated cerebral microvascular ACE was measured using two methods, enzyme kinetic assay or radioligand binding assay. RESULTS: In SHR, cerebral microvessel ACE was of similar activity and concentration and had similar ligand binding affinities to WKY rats. Plasma ACE activity was significantly elevated in WKY rats compared with SHR. CONCLUSION: Cerebral microvascular ACE is similar in SHR and WKY rats. Microvascular ACE is unlikely to participate in the pathogenesis or complications of hypertension in this model.     

A treatment with rosuvastatin induced a reduction of arterial pressure and a decrease of oxidative stress in spontaneously hypertensive rats

The aim of this study was to appreciate consequences of rosuvastatin administration on hemodynamic function, vascular oxidative stress and ischemia/reperfusion disorders in normotensive and hypertensive rats. At 10 weeks of age, spontaneously hypertensive rats (SHR, n=20) and normotensive Wistar Kyoto male rats (WKY, n=20) were divided into four groups and given, either vehicle or 10 mg/kg/day of rosuvastatin by gavage for 3 weeks. Systolic blood pressure was assessed every week. At the end of these treatments, vascular NADPH oxidase activity was evaluated by chemiluminescence (lucigenin 0.5 microM). Hearts were isolated and perfused according to the Langendorff method and were subjected to 30 min of global ischemia. Reactive oxygen species (ROS) produced during reperfusion were quantified by electron spin resonance (ESR) spectroscopy using a spin probe (CP-H, 1 mM). After one week of treatment, rosuvastatin reduced the arterial pressure in SHR rats (180.3 +/- 2.1, SHR vs 169.7 +/- 2.3 mmHg, SHR+rosuvastatin; p < 0.01), without lowering plasma cholesterol levels; these effects were not observed in WKY. NADPH activity was 25% higher in control SHR rat aortas compared to control WKY, and was reduced by rosuvastatin in SHR rats. In isolated rat hearts subjected to ischemia/reperfusion sequences, there was a deterioration in functional parameters in control SHR compared to control WKY hearts. Rosuvastatin decreased post-ischemic contracture in WKY hearts by 50% (41.5 +/- 7.5, WKY control vs 18.4 +/- 4.6 mmHg, WKY+rosuvastatin; p < 0.01) and increased left ventricular developed pressure. This beneficial effect was accompanied by a decrease in ROS detected by ESR during reperfusion (312.5 +/- 45.3, WKY control; vs 219.3 +/- 22.9 AUC/mL, WKY+rosuvastatin; p < 0.05). In conclusion, these results are in accordance with the hypothesis that oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases including hypertension, and demonstrate the beneficial effects of rosuvastatin.     

Thymectomy delays the development of hypertension in Okamoto spontaneously hypertensive rats

Previous studies in rats have demonstrated that immune system dysfunction contributes to the aetiology of spontaneous hypertension. Chronic immunosuppression with cyclophosphamide attenuated the level of hypertension in Okamoto spontaneously hypertensive rats (SHR) by approximately 50%. Also, neonatal thymic implants delayed the development of spontaneous hypertension and significantly attenuated its level at the age of 22 weeks in SHR. In the present study, the effect of thymectomy at the age of 4 weeks on blood pressure was investigated in SHR and Wistar-Kyoto (WKY) rats. The removal of the thymus gland in 4-week-old SHR produced a significant reduction in systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) when rats were 16-19 weeks old, while no pressure reduction was observed in WKY rats. The decrease in arterial pressure of 16-week-old SHR was associated with a significant reduction in lymphocyte count at this age as compared with the control group. In 1-year-old SHR, thymectomized at the age of 4 weeks, there was no significant difference in arterial pressure or lymphocyte count compared with controls. These data support the hypothesis that an immune imbalance may be important in the development of spontaneous hypertension. We conclude that thymectomy at a young age (4 weeks) delays the development of hypertension in SHR.     

Prevention of coronary vasodilator reserve decrement in spontaneously hypertensive rats

Spontaneously hypertensive rats (SHR) demonstrate an elevated minimal coronary vascular resistance by the seventh month of age. In an attempt to determine the role of long-standing hypertension in the etiological process of the elevated minimal coronary vascular resistance, we treated SHR and normotensive Wistar-Kyoto rats (WKY) with the vasodilator hydralazine from the time of weaning (1 month) until they were 7 to 8 months of age. The animals were instrumented 24 hours after their last drug dose and then studied on the following day. Using microspheres we measured myocardial perfusion in conscious rats at rest and during maximal coronary dilation induced with dipyridamole infusion. Hydralazine maintained arterial blood pressures in the normotensive range throughout the experimental period, but had little effect on left ventricular weight/body weight ratios (control SHR = 2.95 +/- 0.07, treated SHR = 2.73 +/- 0.08, control WKY = 2.39 +/- 0.09, mean +/- SEM). In treated SHR, left ventricular minimal coronary vascular resistance (per 100 g of tissue) was markedly lower (0.10 +/- 0.01) than in the controls (0.16 +/- 0.01) and not significantly different from that of WKY (0.11 +/- 0.01). Similar differences were noted in the nonhypertrophic right ventricle (treated SHR = 0.08 +/- 0.01, control SHR = 0.16 +/- 0.01, control WKY = 0.10 +/- 0.01). Total minimal coronary vascular resistance was also lower in both ventricles of the treated SHR compared with their nontreated controls. In WKY, hydralazine treatment significantly reduced blood pressure and total minimal coronary vascular resistance (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Elastic properties and composition of the aortic wall in old spontaneously hypertensive rats.

We hypothesized that age-linked changes in the composition and elastic properties of the arterial wall occur earlier in hypertensive than in normotensive rats. We evaluated the consequences of hypertension and aging on aortic mechanics, geometry, and composition in 3-, 9-, and 15-month-old awake Wistar-Kyoto rats (WKY) (normotensive) and spontaneously hypertensive rats (SHR) (hypertensive). The elastic modulus of the thoracic aorta, calculated from aortic pulse wave velocity and geometry, was higher in young and adult SHR than in age-matched WKY, as was wall stress; however, isobaric pulse wave velocity and pulse wave velocity-pressure curves were similar. Elastic modulus, isobaric pulse wave velocity, and the slope of the pulse wave velocity-pressure curve dramatically increased in old SHR compared with age-matched WKY; there was no further elevation of blood pressure or wall thickness. Fibrosis did not develop with age in SHR, and the ratio of elastin to collagen decreased in a similar fashion with aging in both strains. In conclusion, although elastic properties of the aortic wall are not intrinsically modified in young and adult SHR in comparison to age-matched WKY, aging is associated with a dramatic stiffening of the aortic wall in old SHR but not in WKY. Changes in blood pressure, aortic wall geometry, or scleroprotein composition do not appear to explain this age-linked aortic stiffening in SHR, suggesting that other mechanisms of disorganization of the media may be involved.     

A comparison of CNS angiotensin II binding in the hypothalamus-thalamus-septum-midbrain region of developing spontaneously hypertensive and normotensive rats

Specific angiotensin II (ANG II) binding was studied in brain homogenates from the hypothalamus-thalamus-septum-midbrain (HTSM) region of age-matched 4-, 8-, 12- and 16-week spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using 125I-angiotensin II. Scatchard analysis revealed that the dissociation constants (Kd) ranged from 0.36 to 0.73 nmol/l, although these values were not significantly different at any given age period between the SHR and WKY rats. In contrast, a statistically significant increase in ANG II receptor binding was seen between the SHR and WKY rat at 4 weeks of age. However, this difference was not observed at older age periods. Furthermore, both the SHR and WKY rat showed a decrease in ANG II receptor levels during development, with the most marked reductions occurring between 12 and 16 weeks of age for both strains. These findings suggest that ANG II receptors in the HTSM region of both the SHR and WKY rat are down-regulated during development, that receptor loss is more significant in the SHR than in its normotensive control and that binding capacity differences between the two strains are only seen before the onset of measureable increases in the arterial pressure of the SHR. We conclude that there is a significant difference in the ANG II binding capacity during the development of hypertension in the SHR as compared with the WKY rat and therefore it may play a role in the pathogenesis of this disorder.     

CHRONIC BLOCKADE OF HIPPOCAMPAL KAPPA RECEPTORS INCREASES ARTERIAL PRESSURE IN CONSCIOUS SPONTANEOUSLY HYPERTENSIVE RATS BUT NOT IN NORMOTENSIVE WISTAR KYOTO RATS

Previous studies in this laboratory have shown that dynorphins acting on hippocampal kappa opioid receptors in rat brain exert a restraining influence on arterial blood pressure and that a relative deficiency of their production in the spontaneously hypertensive rat (SHR) may be involved in SHR hypertension. Kappa receptor blockade should therefore exacerbate hypertension in SHR. We explored the latter possibility by chronic unilateral infusion of nor-binaltorphimine dihydrochloride (nor-BNI), a selective kappa receptor antagonist, into the right dorsal hippocampus of conscious SHR and normotensive Wistar-Kyoto (WKY) controls over a 14 day period. Additional controls consisted of similar hippocampal infusions of equivalent volumes of drug vehicle in both rat strains. Mean arterial pressure (MAP) and heart rates (HR) were determined in each animal once daily by the tail cuff method during this period. Nor-BNI induced a sustained increase in the basal high level of MAP in SHR from 132 ± 8 to 150 ± 10 mmHg throughout the 14 days and an increased HR from 427 ± 17 to 477 ± 30 on day 3 to 5 following the drug. By contrast, nor-BNI had no significant effects on either MAP or HR in WKY rats and control infusions of drug vehicle were similarly without effect in both strains. The results support our previous suggestion that the kappa opioid system of the hippocampus ordinarily restrains arterial blood pressure in SHR since prolonged hippocampal kappa receptor blockade results in augmented hypertension in this strain.     

Effects of chronic N-acetylcysteine treatment on the actions of peroxynitrite on aortic vascular reactivity in hypertensive rats.

BACKGROUND: Peroxynitrite (ONOO-), the product of superoxide and nitric oxide, seems to be involved in vascular alterations in hypertension. OBJECTIVES: To evaluate the effects of ONOO- on endothelium-dependent and independent aortic vascular responsiveness, oxidized/reduced glutathione balance (GSSG/GSH), malondialdehyde aortic content, and the formation of 3-nitrotyrosine (3-NT), a stable marker of ONOO-, in N-acetylcysteine (NAC)-treated normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). RESULTS: In SHR only, NAC significantly reduced heart rate and systolic, but not diastolic, blood pressure. It also improved endothelium-dependent aortic relaxation in SHR, but not after exposure to ONOO-. Endothelium-dependent and independent aortic relaxations were markedly impaired by ONOO- in both strains of rat. NAC partially protected SHR against the ONOO- -induced reduction in endothelium-independent relaxation. Aortic GSSG/GSH ratio and malondialdehyde, which were higher in SHR than in WKY rats, showed a greater increase in SHR after exposure to ONOO-. NAC decreased GSSG/GSH and malondialdehyde in both strains of rat before and after exposure to ONOO-. The 3-NT concentration, which was similar in both strains of rat under basal conditions, was greater in SHR than in WKY rats after the addition of ONOO-, with a reduction only in NAC-treated SHR. CONCLUSIONS: These findings suggest an increased vulnerability of SHR aortas to the effects of ONOO- as compared with those of WKY rats. The selective improvements produced by NAC, in systolic arterial pressure, heart rate, aortic endothelial function, ONOO- -induced impairment of endothelium-independent relaxation, aortic GSSG/GSH balance, malondialdehyde content and 3-NT formation in SHR suggest that chronic administration of NAC may have a protective effect against aortic vascular dysfunction in the SHR model of hypertension.     

Pleural protein concentration and liquid volume in spontaneously hypertensive rats

To determine the effect of systemic vascular hypertension on fluid balance in the pleural space, we studied the spontaneously hypertensive rat (SHR) and its genetic normotensive control, the Wistar-Kyoto rat (WKY). We measured arterial and venous pressures, total protein and albumin concentrations of pleural liquid and plasma, pleural space thickness, and pleural surface pressure in SHR and WKY that were matched for weight (260-300 g). Protein concentration was measured by a manual Biuret test and albumin concentration was measured by the bromcresol green colorimetric method. Pleural liquid thickness was measured in situ using light microscopy. Pleural surface pressure was assumed to equal pleural liquid pressure. In the SHR, total protein and albumin concentrations in pleural liquid were lower than in WKY, and pleural space thickness was larger in SHR than in WKY. These results are consistent with a higher capillary pressure and greater fluid filtration in SHR.