Acute hemodynamic effects of ethanol in conscious spontaneously hypertensive and normotensive rats

This study investigated the differential hemodynamic effects of small to high doses of ethanol in conscious age-matched spontaneously hypertensive rats (SHRs) and Wistar Kyoto rats (WKYs). Changes evoked by ethanol (0.25, 0.5, or 1 g/kg, i.v.) or equal volume of saline in mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR) were followed for 90 min in the two rat strains. The baseline MAP (163 +/- 4 vs. 113 +/- 2 mm Hg) of SHRs was significantly (p < 0.05) higher, compared with WKYs due mainly to the presence of an elevated TPR 13.82 +/- 0.12 vs. 2.51 +/- 0.09 mm Hg/ml/min/100 g, p < 0.05) in SHRs. In both rat strains, all doses of ethanol produced immediate increases in MAP at 1 min, after which the MAP responses varied and depended on the rat strain and dose of ethanol used. In WKYs, 0.25 g/kg ethanol had no effect on MAP, but caused significant decreases in CO and SV and increased HR. Ethanol (0.5 and 1 g/kg) produced a short-lived (10 min) and dose-related increase in MAP. The higher dose (1 g/kg) of ethanol elicited significant (p < 0.05) increases in TPR that were counterbalanced by concomitant decreases in CO and SV. In SHRs, the two higher doses (0.5 and 1 g/kg) of ethanol elicited significant (p < 0.05) decreases and increases in MAP, respectively, compared with control (saline-treated) values. The pressor response to the 1 g/kg dose of ethanol was associated with an increase in TPR that achieved a statistical significance (p < 0.05) at 50 and 80 min after ethanol administration. HR was significantly (p < 0.05) reduced by the two higher doses of ethanol, whereas SV and CO were not changed. Blood ethanol concentrations measured 10, 30, and 60 min after ethanol administration were similar in SHRs and WKYs. These findings suggest that acute administration of ethanol to conscious rats elicits hemodynamic responses that are strain- and dose-dependent. In contrast to a short-lived and dose-related pressor response in WKYs, ethanol (0.5 and 1 g/kg) elicited opposite and longer lasting effects on MAP (decreases and increases, respectively) in SHRs. In both rat strains, the pressor response to the higher dose of ethanol was associated with an increase in TPR; an effect that was compromised by a concomitant decrease in CO in WKYs but not SHRs.     

Blood pressure responses of conscious normotensive and spontaneously hypertensive rats to intracerebroventricular and peripheral administration of captopril

In conscious spontaneously hypertensive rats, intraxerebroventricular injection of captopril (2 mg/kg) resulted in a rapid hypotensive response that lasted several hours. The same dose given by intracerebroventricular injection had no significant effect on blood pressure (BP) of normotensive Wistar-Kyoto (WK) rats over 7 hours. There was no significant change in BP of conscious spontaneously hpertensive rats (SHR) in response to intracerebroventricular injection of vehicle and only a transitory fall in BP in response to intravenous injection of captopril (2 mg/kg). There was no significant differences between plasma renin activity (PRA) of conscious normotensive WKY rats and the PRA of SHR. These results suggest biochemical differences between the brains of SHR and normotensive WKY control rats. These differences could involve the brain renin-angiotensin system or other neuropeptides.     

Comparative effects of captopril and MK 421 on sympathetic function in spontaneously hypertensive rats

The effects of captopril and MK 421, both orally active angiotensin-converting enzyme inhibitors, on sympathetic function in the pithed spontaneously hypertensive rat were examined. Captopril (100 mg/kg orally) signif icantly inhibited pressor responses to sympathetic nerve stimulation and norepinephrine whereas MK 421 (10 and 100 mg/kg orally) was without effect. Both drugs abolished the angiotensin l response without affecting that to angiotensin II. Because these doses of MK 421 are antihypertensive in the Spontaneously hypertensive rat, it is concluded that inhibition of sympathetic function plays no role in its effect. The role of the sympatholytic action of captopril in its antihypertensive action remains unclear.     

Cerebrovascular aspects of converting-enzyme inhibition I: Effects of intravenous captopril in spontaneously hypertensive and normotensive rats

The cerebrovascular effects of converting enzyme inhibition were examined in normotensive and hypertensive rats. Cerebral blood flow was measured using the intracarotid 133xenon injection method in halothane/nitrous oxide anaesthetized animals. The main finding was that following intravenous administration of captopril (10 mg/kg), cerebral blood flow autoregulation was markedly altered. Although cerebral blood flow was unchanged from baseline levels, both the lower and upper limits of autoregulation were reset to lower mean arterial pressure and the autoregulatory plateau shortened. The lower limit was shifted 20-30 mmHg, the upper limit 50-60 mmHg, and the plateau shortened by 20-40 mmHg. The effect was interpreted as being a consequence of compensatory autoregulatory constriction of small resistance vessels in the brain following captopril-induced dilatation of large resistance vessels. It was inferred that locally produced angiotensin II might play a role in the resistance of large cerebral arteries.     

Calcitonin gene-related peptide in normotensive and spontaneously hypertensive rats

Using specific radioimmunoassay, radioimmunoreceptor analysis and gel filtration, we found that calcitonin gene-related peptides (CGRP) were distributed in various tissues of normotensive rat (WKY) and spontaneously hypertensive rat (SHR), the highest content was in the lumbar spinal cord (1197 +/- 94.8 pg/mg tissue), the lowest in the auricle (15.0 +/- 2.1 pg/mg tissue). Compared with WKY, the plasma CGRP concentration decreased and the CGRP content in abdominal aorta and hypothalamus increased in SHR. By gel filtration, it showed that only one major molecular form of CGRP was present in the tissues. The CGRP specific binding sites were present both in SHR and WKY hearts, but the number of CGRP binding sites in SHR heart was higher and the binding affinity lower than those in WKY heart. Besides, CGRP can reduce the mean arterial pressure (MAP) in the SHR in a dose-dependent way. The above data indicated that CGRP may play an important role in the pathogenesis of hypertension and exert possibly a therapeutic effect on hypertension.     

Cardiac reflexes in normotensive and spontaneously hypertensive rats.

Characteristics of left atrial receptors were studied in normotensive control (Wistar) and spontenaously hypertensive rats. The left atrial pressure was chronically elevated in spontaneously hypertensive rats and at the end of the expiratory phase was 10.3 mm Hg as compared with 4.6 mm Hg in normotensive control rats. The thresholds of the receptor endings were twice as high in the hypertensive as in the normotensive rats (10.2 and 4.6 mm Hg, respectively). In other experiments the reflex inhibition of renal sympathetic outflow was studied during plasma infusion in baroreceptor denervated normotensive and hypertensive rats was was inhibited at a lower left atrial pressure in the former. These differences are attirubted to decreased distensibility of the left atrium in spotaneously hypertensive rats. The reflex splanchnic nerve inhibition with volume load also was recorded in awake rats. At a 10 percent increase in blood volume, splanchnic outflow was more significantly decreased in spotaneously hypertensive than in normotensive rats. The mechanism underlying such a hyperreactive volume receptor response is unknown, but a less distensible venous system, centrally or peripherally, might be a contributing factor.     

Differential hypertrophic effects of cardiotrophin-1 on adult cardiomyocytes from normotensive and spontaneously hypertensive rats

Cardiotrophin-1 (CT-1) produces longitudinal elongation of neonatal cardiomyocytes, but its effects in adult cardiomyocytes are not known. Recent observations indicate that CT-1 may be involved in pressure overload left ventricular hypertrophy (LVH). We investigated whether the hypertrophic effects of CT-1 are different in cardiomyocytes isolated from adult normotensive and spontaneously hypertensive rats (SHR). Hypertrophy was evaluated by planimetry and confocal microscopy, contractile proteins were quantified by Western blotting and real-time RT-PCR, and intracellular pathways were analyzed with specific chemical inhibitors. CT-1 increased c-fos and ANP expression (p<0.01) and cell area (p<0.01) in cardiomyocytes from both rat strains. In Wistar cells, CT-1 augmented cell length (p<0.01) but did not modify either the transverse diameter or cell depth. In SHR cells, CT-1 increased cell length (p<0.05), cell width (p<0.01) and cell depth, augmented the expression of myosin light chain-2v (MLC-2v) and skeletal alpha-actin (p<0.01) and enhanced MLC-2v phosphorylation (p<0.01). The blockade of gp130 or LIFR abolished CT-1-induced growth in the two cell types. All distinct effects observed in cardiomyocytes from SHR were mediated by STAT3. Baseline angiotensinogen expression was higher in SHR cells, and CT-1 induced a 1.7-fold and 3.2-fold increase of angiotensinogen mRNA in cardiomyocytes from Wistar rats and SHR respectively. In addition, AT1 blockade inhibited the specific effects of CT-1 in SHR cells. Finally, ex vivo determinations revealed that adult SHR exhibited enhanced myocardial CT-1 (mRNA and protein, p<0.01), increased cell width (p<0.01) and concentric LVH compared with pre-hypertensive SHR. These findings reveal a specific cell-broadening effect of CT-1 in cardiomyocytes from adult SHR and suggest that the hypertensive phenotype of these cells may influence the hypertrophic effects of CT-1, probably by means of an exaggerated induction of angiotensinogen expression. We suggest that CT-1 might facilitate LVH in genetic hypertension through a cross-talk with the renin-angiotensin system.     

Effect of low doses of angiotensin II perfusion on the hypotensive action of captopril in anaesthetized normotensive and spontaneously hypertensive rats

The effect of intravenous (i.v.) captopril on mean arterial blood pressure (MABP) of anaesthetized normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats perfused i.v. with two doses of angiotensin II (ANG II; 2.9 and 5.8 pmol/kg per min) was studied to determine the role of the suppression of plasma ANG II in the hypotensive action of captopril. The reduction of MABP by captopril was attenuated in WKY and abolished in SHR by the highest dose of ANG II; it was unchanged in WKY and attenuated in SHR by the lowest dose of ANG II. The suppression of plasma ANG II thus explains a minor part of the acute reduction of MABP by captopril in WKY and a major part of this action in SHR. Plasma ANG II contributes to the maintenance of high blood pressure in SHR.     

Involvement of Ras-regulated myosin light chain phosphorylation in the captopril effects in spontaneously hypertensive rats

BACKGROUND: Early treatment with captopril prevents the development of hypertension by inhibiting the generation of angiotensin II and smooth muscle contraction. Although smooth muscle contraction is regulated by myosin light chain phosphorylation (MLC-P), the role of MLC-P in captopril effects in hypertension has not been described. Therefore, we treated spontaneously hypertensive rats (SHR) with captopril and investigated the effects of this agent on downstream signaling. METHODS: Male SHR (n = 12) were treated with captopril (3.7 mmol/L in drinking water) beginning in utero and continuing up to 12 weeks of age. Age- and sex-matched untreated SHR and Wistar-Kyoto (WKY) rats were used as controls. Rats were split into three subgroups and were sacrificed at 12, 18, or 24 weeks of age. Systolic blood pressure, left ventricular weight, and body weight were measured. Mesenteric arteries were removed for histologic and biochemical studies. RESULTS: At 12 weeks, captopril significantly decreased systolic blood pressure (from 198 +/- 10 to 125+/-16 mm Hg), reduced left ventricular weight-to-body weight ratios (from 2.94 +/- 0.06 to 2.17 +/- 0.08 mg/g), and prevented vascular remodeling in mesenteric arteries in SHR. Ras expression, extracellular receptor kinase phosphorylation (ERK-P), myosin light chain kinase (MLCK) expression, and MLC-P were all significantly increased in mesenteric arteries in untreated SHR compared with WKY rats. Early captopril treatment in SHR significantly inhibited Ras and MLCK expression at all ages and decreased ERK-P and MLC-P at 12 and 18 weeks in mesenteric arteries. CONCLUSIONS: These data demonstrate that the antihypertensive effects of captopril are correlated with inhibition of Ras-regulated ERK activation, MLCK expression, and MLC-P.     

Aspirin enhances the antihypertensive effect of captopril in spontaneously hypertensive rats

Activation of renal or vascular prostaglandin mechanisms (or both) has been proposed to contribute to the antihypertensive action of captopril. In conscious spontaneously hypertensive rats (SHR) studied in the established phase of hypertension, the blood pressure-lowering effect of captopril, 30 mg/kg/12 hr p.o. given for 7 days, was greatly enhanced by the addition of aspirin, 200 mg/kg/day s.c. Systolic blood pressure decreased from 185 +/- 6 and 182 +/- 4 to 135 +/- 3 mm Hg in rats treated, respectively, with captopril and aspirin or captopril alone, and was unaltered by either vehicle or aspirin alone. Water intake was inconsistently affected by captopril but was increased (p less than 0.01) by aspirin and was even higher after captopril-aspirin treatment (p less than 0.01). Urine volume was elevated in all 3 drug-treated groups, increasing threefold after captopril-aspirin treatment. Excretion of sodium and potassium was unchanged by any treatment regimen. In the vehicle group, prostaglandin F2 alpha excretion, measured by radioimmunoassay, ranged between 65 and 93 ng/8 hr and was twofold to fourfold higher than that of prostaglandin E2. Prostaglandin F2 alpha was unaffected during captopril treatment, whereas prostaglandin E2 excretion decreased to 12 +/- 2 ng/8 hr (p less than 0.01) by Day 7. Long-term aspirin treatment, either with or without captopril, did not cause sustained inhibition of renal prostaglandin excretion, although a transient effect occurred within the first four hours of administration. These results indicate 1) aspirin potentiates the blood pressure-lowering effect of captopril in SHR, an effect that is associated with a threefold increase in urine flow.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urapidil in normotensive and spontaneously hypertensive rats: the effects on systemic and regional haemodynamics and cardiac mass

The effects of treatment for three weeks with urapidil (10 mg/kg p.o. twice daily) on systemic and regional haemodynamics and cardiac mass were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Urapidil decreased mean arterial pressure and total peripheral resistance index (176 +/- 3 versus 145 +/- 5 mmHg and 0.61 +/- 0.02 versus 0.49 +/- 0.02 units, respectively; each P less than 0.01) in SHR without affecting heart rate, cardiac index or cardiac mass. No systemic haemodynamic changes were observed in WKY rats. All organ vascular resistances decreased significantly in SHR and blood flow increased to skin (P less than 0.01) and kidneys (P less than 0.05). These data indicate that urapidil is a potent antihypertensive agent in SHR which reduced mean arterial pressure through a decreased total peripheral resistance that was distributed throughout all circulations. Despite these haemodynamic changes, cardiac mass did not change.     

alpha-Adrenergic receptors in cerebral microvessels of normotensive and spontaneously hypertensive rats

In rat cerebral microvessels, we characterized alpha 1- and alpha 2-adrenergic receptors, using [3H]prazosin and [3H]-p-amino-clonidine as radioligands. [3H]Prazosin binding to the cerebral microvessels was saturable and of high affinity (dissociation constant of 78 pM), with a maximum binding of 48 fmol/mg protein. [3H]Prazosin binding reached equilibrium within 15 minutes and was dissociated by the addition of 10 microM phentolamine. The inhibitory effects of isomers of norepinephrine and epinephrine on the binding showed that l-isomers were over 10 times more potent than d-isomers. [3H]-p-Amino-clonidine binding to the cerebral microvessels was saturable and of high affinity (KD = 0.61 nM) with a Bmax of 73 fmol/mg protein. The binding reached equilibrium within 30 minutes, and was dissociated by the addition of 100 microM l-norepinephrine. l-Isomers of norepinephrine and epinephrine were over 10 times more potent than d-isomers in displacing the binding. Thus, both [3H]prazosin and [3H]-p-amino-clonidine bindings to the cerebral microvessels were characterized by saturability, high affinity, reversibility, and stereo-specificity. Furthermore, the specificity of both binding sites was pharmacologically evaluated by the inhibitory effects of various adrenergic agonists and antagonists on the bindings. These data indicate the existence of alpha-adrenergic receptors in the cerebral microvessels and are consistent with the hypothesis that the cerebral microcirculation is regulated by adrenergic innervation. Furthermore, the receptors were measured in cerebral microvessels of spontaneously hypertensive rats and Wistar-Kyoto controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

The variability of baroreflex sensitivity in juvenile, spontaneously hypertensive rats

In this study the baroreflex sensitivity of conscious, juvenile, spontaneously hypertensive rats (SHRs) was compared. The study population consisted of 19 eight-week-old male SHRs. The baroreflex sensitivity was quantified as the derivative of the variation in heart rate (HR) and the variation of mean arterial pressure (baroreflex sensitivity = ΔHR/ΔMAP). MAP was manipulated with sodium nitroprusside (SNP) and phenylephrine (PHE), administered via an inserted cannula in the right femoral vein. The SHRs were divided into four groups: (1) low bradycardic baroreflex (LB) where the baroreflex gain (BG) was between 0 and -1 bpm/mmHg with PHE; (2) high bradycardic baroreflex (HB), where the BG was < -1 bpm/mmHg with PHE; (3) low tachycardic baroreflex (LT) where the BG was between 0 and 3 bpm/mmHg with SNP; (4) high tachycardic baroreflex (HT) where the BG was > 3 bpm/mmHg with SNP. We noted that 36.8% of the rats presented with an increased bradycardic reflex, while 27.8% demonstrated an attenuated tachycardic reflex. No significant alterations were noted regarding the basal MAP and HR. There were significant differences in the baroreflex sensitivity between SHRs in the same laboratory. One should be careful when interpreting studies employing the SHR as a research model.     

Ischemic preconditioning maintains cardioprotection in aging normotensive and spontaneously hypertensive rats

We determined whether ischemic preconditioning could reduce infarct size and improve cardiac function in both aging normotensive Wistar–Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). The left anterior descending coronary artery was occluded for 1 h followed by 3 h reperfusion in aging (∼16 months old) SHR rats and age-matched WKY rats. Hearts were either preconditioned or not (control group) prior to 1 h of coronary artery occlusion. The preconditioning regimen consisted of three cycles of 3 min occlusion followed by 5 min reperfusion applied prior to the subsequent 1 h occlusion. In WKY (n = 12 each group), the risk zone was similar in the control (51 ± 2%) and preconditioned group (46 ± 2%; p = 0.1). Preconditioning significantly reduced infarct size (as a percentage of the ischemic risk zone) (24 ± 6%) compared to controls (51 ± 5%; p = 0.0026). In SHR rats (n = 9 each group), the risk zone was smaller in the preconditioning group (41 ± 3%) than in the control group (51 ± 3%; p = 0.035). Infarct size (as % of ischemic risk zone) was also significantly reduced in the preconditioned group (13 ± 4%) compared to controls (62 ± 5%; p < 0.0001). For both WKY and SHR rats, for any sized risk zone the infarct size was smaller in preconditioned hearts compared with the control hearts. Preconditioning improved aspects of LV function during ischemia and reperfusion phase in SHR rats, but these benefits were not observed in the WKY rats. Preconditioning maintains powerful cardioprotection in aging normotensive hearts as well as aging hypertrophied hearts.     

Blood pressure and salt appetite of cross-suckled spontaneously hypertensive and normotensive rats

An examination has been made of the blood pressure (BP), saline preference and circulating renin-angiotensin system of spontaneously hypertensive rats (SHR) of the Okamoto strain, normotensive Sprague-Dawley (SD) rats, SHR suckled from immediately after birth on an SD foster mother (SHR-on-SD) and SD cross-suckled on an SHR foster mother (SD-on-SHR). While the BP of SD-on-SHR was not significantly different from that of control SD, SHR-on-SD had significantly lower BP than SHR suckled on their natural mothers. In two-bottle preference tests, neither the saline preference nor total fluid intake of cross-suckled SHR was significantly different from that of SHR controls. While the total fluid intake of SD-on-SHR was not different from that of SD controls, the saline preference of cross-suckled SD was significantly lower than that of control SD. The heart, adrenal and kidney weights of SHR were significantly greater than those of SD, but there were no significant differences between cross-suckled rats and their respective controls. There were no significant differences in plasma renin activity (PRA) or angiotensin converting enzyme (ACE) activity between any groups and these variables did not correlate with each other, with BP or with saline preference. Thus, some factor transferred from the SHR mother postnatally is required for full expression of the elevated BP, but not the exaggerated saline preference of the SHR. Conversely, the saline preference of SD, but not the BP, is altered by cross-suckling.     

Metabolic, hemodynamic, and cardiac effects of captopril in young, spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHR) demonstrate elevated blood pressure, cardiac hypertrophy, glucose intolerance, and insulin resistance compared with age-matched Wistar-Kyoto rats (WKY). We investigated concurrent effects of captopril on blood pressure, cardiac mass, myocardial enzyme activities, glucose tolerance, and insulin action in young male SHR. At 10 weeks of age, SHR were randomized into two groups, one receiving distilled water, the other a captopril solution (50 mg/kg body weight/day). We also examined age-matched WKY receiving distilled water. Blood pressure was measured by tail-cuff during the 4-week treatment period and oral glucose tolerance was tested at the end of treatment. Hearts were weighed and ventricular tissue was assayed for activities of 3-hydroxyacyl-CoA dehydrogenase, citrate synthase, and hexokinase. Growth rates were similar between captopril-treated and control SHR, but less than those of WKY. Captopril reduced blood pressure (134 +/- 8 v 177 +/- 8 mm Hg, P < .05) and left ventricular mass (-18%, P < .05) in SHR. Cardiac enzyme activities also changed with captopril treatment, reflecting an increased capacity for beta-oxidation of fatty acids and reduced potential for glucose phosphorylation in the left ventricle of SHR. Serum concentrations of glucose, insulin, and free fatty acids after a brief fast and in response to oral glucose were not different after captopril treatment, suggesting no improvement in insulin action or glucose tolerance. In summary, treatment of young male SHR with captopril reduces blood pressure and cardiac mass, and promotes a small but significant increase in cardiac capacity for oxidation of fatty acids and reduction of glucose phosphorylation. In contrast, metabolic effects of captopril on oral glucose tolerance and insulin action were not evident.     

Acute effects of salbutamol on arteriolar vasodilatation and blood pressure in spontaneously hypertensive rats

The acute effects of salbutamol, a β₂ agonist, on arteriolar vasodilatation and blood pressure were studied in WKY and SHR rats. The cremaster muscle was prepared for in vivo microscopy and the femoral artery cannulated for administration of salbutamol (0.001- to 4.0-μg doses). Systemic mean arterial pressures were measured from the carotid artery. Changes in arteriolar diameter were recorded on videotape and analyzed using variable resistance calipers to trace the changes in diameter. In both WKYs and SHRs salbutamol induced dose-dependent vasodilatations, the magnitudes of which were inversely related to the resting diameter. Among arterioles 35 μm or less in diameter, the SHRs exhibited significantly greater percentage vasodilatations. Vasodilatation among arterioles greater than 35 μm was strongly attenuated at all doses in both WKYs and SHRs. These vasodilatory responses were accompanied by dose-dependent decreases in the mean arterial pressure. At all doses the absolute pressure drop was greater in the SHR, although the percentage decreases were similar. Both the vasodilatations and blood pressure decreases were blocked by propranolol. This enhanced vasodilatory capacity to β₂ stimulation by the smaller SHR arterioles may serve as part of a compensatory mechanism to maintain sufficient blood flow regulation in the face of a reduced vascular density.     

Long-term effects of captopril on passive sodium permeability and contractility in vascular smooth muscles of spontaneously hypertensive rats

Long-term effects of captopril on passive sodium permeability and cellular sodium concentration in the aorta of spontaneously hypertensive rats were examined in terms of contractile properties of the muscle. In cold lithium solution, cellular sodium in the aorta isolated from spontaneously hypertensive rats leaked more rapidly than did that isolated from Wistar Kyoto rats (WKY), suggesting an increased sodium permeability in the aorta of spontaneously hypertensive rats. Six weeks of treatment with captopril reduced the increased sodium permeability after hydralazine had failed. Inhibition of the sodium pump by incubating the aorta in potassium-free solution produced a slowly developing contraction which was associated with accumulation of cellular sodium. Both the magnitude of contraction and the accumulation of sodium during exposure to potassium-free solution for 1 hour were significantly less in the aorta isolated from spontaneously hypertensive rats treated with captopril compared with those from control spontaneously hypertensive rats. These data suggest that after prolonged administration, captopril alters the abnormal sodium permeability of vascular smooth muscle in spontaneously hypertensive rats and that the restoration of normal permeability reduces vascular tone.     

Capillary pressure gradients in cremaster muscle of normotensive and spontaneously hypertensive rats

The purpose of this investigation is to test the hypothesis that capillary pressure gradients are elevated in spontaneously hypertensive rats (SHR) and to determine the mechanism for the elevation. The cremaster muscle was prepared for microscopic examination under chloralose-urethane anesthesia in seven SHR and eight Wistar-Kyoto (WKY) rats 4-6 weeks of age. Capillary hematocrit, diameter, and red cell velocity were measured. Capillary flow induced by a time-varying pressure gradient was treated mathematically. A finite Hankel transformation was applied to the Navier-Stokes equation for capillary vessels. The solution was expressed as a Fourier-Bessel series, and the fluctuation of capillary flow induced by a time-varying pressure gradient was studied. It was shown that if the velocity fluctuation depended only on the pressure gradient, then the velocity fluctuation would be diminished almost instantly after the capillary started to flow. Capillary pressure gradient and shear stress were evaluated according to two different flow models, Newtonian and Casson. The capillary viscosity was obtained from the capillary hematocrit based on the empirical correlation of viscosity vs hematocrit. Calculations based on both flow models indicate that the capillary pressure gradient and shear stress of SHR is higher than in WKY, especially in vessels near 6 microns in diameter. The elevated pressure gradient is due to a combination of reduced capillary density, causing a higher red cell velocity and a tendency toward smaller capillary diameters in the SHR. Capillary hematocrit and viscosity were not elevated in the SHR.     

The vascular response of spontaneously hypertensive and normotensive rats with diabetes mellitus

Streptozotocin-induced diabetes caused an increase in AP and reactivity to noradrenaline in perfused caudal artery of normotensive rats (WKY). In spontaneously hypertensive rats (SHR) diabetes led to an increase in reactivity not only to noradrenaline but also to alpha 1-agonist phenylephrine; a response to endothelium-dependent agent acetylcholine was decreased. Alterations in function of the vascular endothelium may be one of the factors causing elevation of vasoconstriction in diabetes mellitus.