Responses of the basilar artery to products released by platelets during chronic hypertension

The goal of this study was to determine whether responses of the basilar artery to products released by platelets are altered during chronic hypertension. The diameter of the basilar artery was measured using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) (6-8 months old) in response to adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue, U-46619. Dilatation of the basilar artery in response to nitroglycerin was also examined in WKY and SHR. Topical application of ADP (10 and 100 microM) produced only minimal changes in diameter of the basilar artery in WKY (3 +/- 1% and 1 +/- 1%, respectively) and SHR (-0.5 +/- 2% and -2 +/- 3%, respectively) (P greater than 0.05 vs WKY). Nitroglycerin, however, produced potent vasodilatation in WKY and SHR. Constriction of the basilar artery in response to serotonin was potentiated in SHR compared to WKY. Serotonin (0.1 and 1.0 microM) constricted the basilar artery by 11 +/- 2% and 20 +/- 2%, respectively, in WKY and by 29 +/- 3% and 40 +/- 3%, respectively, in SHR (P less than 0.05 vs WKY). In contrast, the thromboxane analogue (U-46619) (0.1 and 1.0 microM) produced similar constriction of the basilar artery in WKY (13 +/- 1% and 18 +/- 2%, respectively) and in SHR (14 +/- 3% and 21 +/- 6%, respectively). Thus, augmented vasoconstriction during chronic hypertension was specific for serotonin. Next, we examined the role of the cyclooxygenase pathway in responses of the basilar artery to ADP and serotonin.(ABSTRACT TRUNCATED AT 250 WORDS)     

The baroreflex contribution to spontaneous heart rhythm assessed with a mathematical model in rats

In Spontaneously Hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats, we quantified the extent to which spontaneous fluctuations of heart period (HP) may be determined from arterial pressure based on linear baroreflex properties. We analyzed time series (30-s length) of low-frequency (<0.8 Hz) fluctuations of HP and mean arterial pressure obtained during quiet wakefulness, rapid-eye-movement sleep (REMS) and non-rapid-eye-movement sleep (NREMS) as well as a control set of surrogate isospectral data with random phase. HP was modeled as the summed output of two parallel linear transfer functions with arterial pressure as input. The mean square difference between modeled and recorded HP was minimized by varying model parameters. The percentage of time series, in which such difference was lower than half the measured HP variance was significantly lower in REMS (6+/-1%, SHR; 5+/-1%, WKY) than either in quiet wakefulness (25+/-2%, SHR; 35+/-3%, WKY) or NREMS (33+/-3%, SHR; 27+/-3%, WKY), and in quiet wakefulness, it was significantly lower in SHR than in WKY. In surrogate data, these percentages were significantly lower than in recorded data during quiet wakefulness and NREMS, but not during REMS. The extent to which linear baroreflex properties explain spontaneous heart rhythm thus depends on the interaction between the behavioral state and the hypertensive disease, and in REMS, may be accounted for by chance couplings between HP and arterial pressure.     

The effect of long-term antihypertensive treatment on medial hypertrophy of cerebral arteries in spontaneously hypertensive rats

The effects of antihypertensive treatment on the structural changes of middle cerebral arteries (MCA) were studied quantitatively and morphometrically in young spontaneously hypertensive rats (SHR). Fifteen male SHR, 10 weeks of age, were divided into control and experimental groups. In the experimental group, the animals were administered hydralazine and guanethidine for the following 10 weeks. At the age of 20 weeks, mean arterial blood pressure of experimental animals was 177 +/- 9 mm Hg (mean +/- SD), being significantly lower than that of 195 +/- 12 mm Hg in control ones. Media thickness of large (external diameter greater than or equal to 200 micron) and medium sized MCA (150-200 micron) in treated SHR was 12.3 +/- 2.8 and 6.3 +/- 1.1 micron, respectively, being significantly smaller than that of 14.0 +/- 2.2 and 8.5 +/- 2.6 micron, respectively, in control SHR. The media cross-sectional area and the ratio of media thickness to external diameter were also significantly reduced by antihypertensive treatment. In the smaller vessels (75-150 micron), however, vascular morphometry revealed no difference between the two groups. Long-term antihypertensive treatment during the early phase of hypertension attenuates the development of medial hypertrophy in large cerebral arteries.     

Effect of hypertension on the integrity of blood brain and blood CSF barriers,cerebral blood flow and CSF secretion in the rat

Hypertension has been related to the development of brain damage, dementia and other CNS dysfunctions. Disruption of the blood-brain barrier (BBB) is thought to contribute to these disorders. In this study, the integrity of both blood-brain and blood-CSF barriers during chronic hypertension was investigated. For this, the entry of [14C]sucrose and of lanthanum into brain tissue, choroid plexus, and CSF was studied. Also brain regional blood flow and brain [14C]sucrose volume of distribution were measured using indicator fractionation and ventriculo-cisternal perfusion methods, respectively. The above measurements were performed in normotensive (WKY) rats and in the spontaneously hypertensive rats (SHR). Choroid plexus and CSF uptakes of [14C]sucrose were found to be significantly greater in SHR compared to WKY rats (P<0.05). Intercellular entry of lanthanum was observed in choroidal tissue of SHR but not in that of WKY rats and at the BBB. Choroid plexus blood flow was significantly greater in SHR, 2.82+/-0.21 ml g(-1) min(-1), compared to 2.4+/-0.08 ml g(-1) min(-1) in WKY (P<0.05). There were no significant differences (P>0.05) in brain % water content and extracellular fluid [14C]sucrose volume of distribution between SHR and WKY rats. However, choroid plexus showed greater % water content in SHR (85.7+/-1.9%) compared to the WKY rats (81.5+/-1.7%). These results suggest that chronic hypertension in SHR may cause more pronounced defects in the integrity of the blood-CSF barrier than in the BBB.     

Regional cerebral blood flow autoregulation in normotensive and spontaneously hypertensive rats--effects of sympathetic denervation

The present study was designed to investigate the effect of acute sympathetic denervation on the regional cerebral blood flow (CBF) autoregulation during acute elevation of blood pressure in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). CBF to the parietal cortex and thalamus was measured by the hydrogen clearance method and, to test autoregulation, systemic arterial blood pressure was elevated by intravenous infusion of phenylephrine. Superior cervical ganglia were removed on both sides to interrupt sympathetic innervation in the deeper structures of the brain. Acute bilateral sympathetic denervation did not alter the resting blood pressure or CBF in either SHR or WKY. In innervated SHR, resting mean arterial pressure (MAP) was 165 +/- 5 mm Hg (mean +/- SEM) and the upper limit of autoregulation in the cortex was 210 +/- 3 mm Hg, which was significantly lower than that in the thalamus (229 +/- 3 mm Hg, p less than 0.02). In bilaterally denervated SHR, the upper limits were lowered to 193 +/- 4 mm Hg in the cortex (p less than 0.02 vs. innervated SHR) and to 207 +/- 5 mm Hg in the thalamus (p less than 0.02 vs. innervated). In WKY, resting MAP was approximately 55 mm Hg lower than that in SHR. Acute denervation reduced the upper limits from 142 +/- 3 mm Hg to 130 +/- 4 in the cortex (p less than 0.05) and from 158 +/- 4 to 145 +/- 4 in the thalamus (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of aging and hypertension on endothelium-dependent vascular relaxation in rat carotid artery

We evaluated the effects of aging and hypertension on endothelium-dependent relaxation of rat common carotid arteries using 14-week-old (young) and 11-month-old (old) Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). Isometric tension of common carotid artery ring segments was measured. With a resting tension of 2.0 g determined from the baseline tension-contraction curves, precontraction was induced by 10(-5) M 5-hydroxytryptamine and endothelium-dependent relaxation was measured by application of either acetylcholine or adenosine 5'-triphosphate (ATP). Mean arterial blood pressure was 73.1 +/- 3.0 mm Hg in WKY and 110.0 +/- 3.1 mm Hg in SHR. These baseline values were significantly different. Acetylcholine-induced maximal relaxations were 70.1 +/- 2.6% of the 5-hydroxytryptamine-induced contraction in young WKY, 45.6 +/- 2.1% in old WKY, 35.1 +/- 1.8% in young SHR, and 21.4 +/- 2.5% in old SHR. On the other hand, ATP-induced relaxations were 52.0 +/- 3.2%, 35.7 +/- 3.8%, 21.7 +/- 3.5%, and 17.0 +/- 1.8% in the groups, respectively. Acetylcholine-induced relaxations were significantly different between WKY and SHR, young and old, independently. On the other hand, ATP-induced relaxations were also significantly different between young and old WKY, although no significant difference was observed between young and old SHR. The fact that endothelium-dependent relaxation of a cephalic artery is impaired in old rats and in hypertensive rats suggests that aging and hypertension are risk factors that may augment the disturbance of the cerebral circulation in pathologic conditions.     

Enhanced renal response to intracerebroventricular angiotensins II and III in spontaneously hypertensive rats.

The acute effects of intracerebroventricular (i.c.v.) administration of angiotensin III (ANG III) on blood pressure (BP) and renal function were investigated in spontaneously hypertensive rats (SHR, n = 31) and Wistar-Kyoto (WKY) normotensive rats (n = 6). ANG II was also administered to the same rats for comparison of its renal effect. BP and renal clearance responses were measured before and during ANG injections. The results showed that i.c.v. injections of 1, 5 and 50 pmol of ANG III did not significantly alter BP in SHR, but a high dose of ANG III (50 pmol) caused a vasopressor effect (7 +/- 4 mmHg) in WKY rats. There were significant increases in renal plasma flow (RPF), glomerular filtration rate (GFR), urine flow, absolute and fractional excretions of sodium and potassium, osmolar clearance and free water reabsorption rate following i.c.v. administration of ANG III in both SHR and WKY rats. However, the enhancement in renal responsiveness to ANG III was greater in SHR than in the WKY group. At 5 pmol of ANG III, the peak increases in GFR (96 +/- 23%), diuresis (316 +/- 102%) and natriuresis (712 +/- 281%) in SHR were significantly greater than those in WKY rats (40 +/- 13%, 152 +/- 89%, 229 +/- 130%, resp.). The renal effect of central ANG III was blocked by i.c.v. ANG III antagonist, [Ile7]-ANG III, but was enhanced by bestatin, an ANG III metabolic enzyme inhibitor. I.c.v. administration of ANG II at 50 pmol increased BP in both SHR and WKY rats (14 +/- 3 and 10 +/- 3 mmHg, resp.). Greater diuretic and natriuretic responses to ANG II were also noted in SHR than in WKY rats. These results indicate that central ANG III is as active as ANG II in modulating renal function. Furthermore, the enhanced renal response to i.c.v. ANGs II and III in SHR suggests a hyperactive central RAS implicated in BP and body fluid regulation in this genetic hypertensive strain.     

Angiotensin II binding sites in the superior cervical ganglia of spontaneously hypertensive and Wistar-Kyoto rats after preganglionic denervation

Angiotensin II binding was higher in superior cervical ganglia of adult spontaneously hypertensive rats (SHR) when compared to ganglia of Wistar-Kyoto (WKY) rats (571 +/- 29 and 375 +/- 9 fmol/mg protein, SHR and WKY, respectively, P less than 0.05). Unilateral preganglionic denervation reduced binding site density in ganglia of WKY (-39%, P less than 0.05 vs sham operated ganglia in WKY), and the decrease of binding sites was larger in SHR (-59%, P less than 0.01, operated vs sham operated ganglia in SHR). Part of the binding sites in the superior cervical ganglia may be present in or be associated to preganglionic nerves, and the number of these sites is higher in SHR.     

Metabolic mapping in the sympathetic ganglia and brain of the spontaneously hypertensive rat

Local rates of glucose utilization in the superior cervical, cardiac, and coeliac ganglia were measured by means of the autoradiographic 2-deoxy-D-[14C]glucose method in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), 32-34, 46-48, and 78-87 days old. Brain glucose utilization was examined in 78-87-day-old SHR and WKY. At 32-34 days (at which time mean arterial blood pressure was normal and similar in both groups of rats), the rates of glucose utilization of all three sympathetic ganglia were the same in both groups. At 46-48 days, despite the fact that blood pressure had risen significantly in SHR (mean +/- SEM, 136 +/- 3 mm Hg, n = 5, compared to 113 +/- 3 mm Hg, n = 5, in the control WKY), glucose utilization was decreased in the cardiac and coeliac ganglia but not in the superior cervical ganglia of the SHR. At 78-87 days, glucose utilization was reduced in all the sympathetic ganglia of the hypertensive rats. These results suggest that the sympathetic system is less active in SHR and indicate that hyperactivity of the sympathetic nervous system is not part of the mechanism of the hypertension. Of 44 structures examined in the central nervous system, only the external cuneate, vestibular, and fastigial nuclei of the SHR exhibited increased rates of glucose utilization, and no changes were found in any of the other structures. These increases are probably not related to the origin or maintenance of the hypertension, inasmuch as lesioning of the vestibular or fastigial nuclei did not decrease blood pressure in the SHR.     

Association between sympathetic nerve activity and cerebrovascular protection in young spontaneously hypertensive rats

The purpose of this study was to determine resting and maximal superior cervical sympathetic nerve activity in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) at five and ten weeks of age as hypertension was developing. Basal cervical sympathetic nerve activity (SNA) of five week SHR was 58 +/- 3 muv* which was significantly elevated over age-matched WKY (SNA = 30 +/- 4 muv, *p less than 0.001) and ten week SHR (SNA = 30 +/- 4 muv, *p less than 0.001) as well as ten week WKY (SNA = 24 +/- 4 muv, *p less than 0.001). Thus, during basal conditions five week SHR nerve traffic was approximately two times that found in age-matched WKY as well as in ten week SHR and WKY. The peak sympathetic nerve activity in response to rapid hemorrhage in five week SHR (215 +/- 16 muv*) was significantly elevated over the maximal response of WKY (140 +/- 23 muv) (*p less than 0.02). Ten week SHR also reached a maximal sympathetic nerve activity (187 +/- 28 muv*) that was significantly elevated over WKY (100 +/- 15 muv) (*p less than 0.02). Thus, both five and ten week SHR had a greater capacity for elevated nerve activity following rapid hemorrhage than age-matched WKY. The elevation in resting cervical sympathetic activity in five week SHR, and the elevated capacity for sympathetic neural response in both five as well as ten week SHR, are consistent with a central nervous system abnormality in SHR that could relate to the previously described protective influence of sympathetic nerves on SHR cerebral blood vessels as hypertension is developing.     

Increased brain uptake and CSF clearance of 14C-glutamate in spontaneously hypertensive rats

Blood-to-brain and blood-to-CSF transport kinetics of 14C-glutamate in the spontaneously hypertensive rats (SHR) were studied using the in situ brain perfusion technique. Also, clearance of 14C-glutamate from CSF of SHR was studied using the ventriculo-cisternal (VC) perfusion technique. Blood-to-brain and blood-to-CSF transport kinetics showed greater rate of maximal transport into both brain and CSF of SHR compared to normotensive Wistar Kyoto (WKY) rats (p>0.05). Uptake into CSF of WKY and uptakes into brains of WKY and SHR did not show any significant diffusion (K(d)) of 14C-glutamate (p<0.05). However, some diffusion of 14C-glutamate only into CSF of SHR was observed, 0.031+0.006 microl min(-1) g(-1). Clearance of 14C-glutamate from CSF was greater in the SHR (28.33+/-6.9 microl min(-1)) compared to that in WKY rats (19.42+/-4.7 microl min(-1)). However, 14C-glutamate uptake by brain from CSF side was not significantly different between SHR and WKY rats (p>0.05). These results suggest that the greater blood-to-brain and blood-to-CSF entry of 14C-glutamate during hypertension may be balanced by greater removal of 14C-glutamate from CSF back to blood.     

Release of glutamate and GABA in the amygdala of conscious rats by acute stress and baroreceptor activation: differences between SHR and WKY rats

To reveal the functional importance of amino acid neurotransmission in the amygdala (AMY) of conscious spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, the in vivo release of glutamate (GLU) and GABA in this brain structure was studied using the push-pull superfusion technique. Basal GLU and GABA release rates in the AMY were comparable in SHR and WKY rats, although arterial blood pressure (BP) in SHR (152+/-6 mmHg) was higher than in WKY rats (102+/-4 mmHg). Neuronal depolarization by superfusion with veratridine enhanced the release of GLU and GABA to a similar extent in both rat strains. On the other hand, exposure to noise stress (95 dB) for 3 min led to a tetrodotoxin-sensitive increase in GLU release in the AMY of SHR, but not WKY rats. The concurrent pressor response to noise was enhanced in SHR as compared to WKY rats. A rise in BP induced by intravenous infusion of phenylephrine for 9 min had no effect on amino acid release in the AMY of both strains. The data suggest an exaggerated stress response of glutamatergic neurons in the AMY of SHR as compared with WKY rats, which might be of significance for the strain differences in the cardiovascular and behavioural responses to stress. The results also show that, in both rat strains, glutamatergic and GABAergic neurons in the AMY are not modulated by baroreceptor activation. Moreover, hypertension in adult SHR does not seem to be linked to a disturbed synaptic regulation of glutamatergic or GABAergic transmission in the AMY.     

Sympathetic inhibition and attenuation of spontaneous hypertension by PVN lesions in rats

To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.     

Effect of immobilization stress on brain polyamine levels in spontaneously hypertensive and Wistar-Kyoto rats

The present study aimed to compare the basal brain polyamine levels and stress-induced brain polyamine level changes in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. For immobilization stress, both strains underwent acute (3 h per day immobilization for 2 days), chronic (3 h per day immobilization for 15 consecutive days), or no immobilization stress (control group). Basal putrescine (PU) levels in frontal cortex and hippocampus of SHR (11.03 +/- 0.81 and 11.36 +/- 0.33 nmol/g tissue, respectively) were significantly higher than WKY rats (6.90 +/- 1.44 and 7.82 +/- 0.71 nmol/g tissue, respectively). However, there were no strain differences in basal spermidine and spermine levels between the two. After acute stress, the PU levels in frontal cortex and hippocampus (15.99 +/- 0.45 and 14.10 +/- 0.95 nmol/g tissue, respectively) were significantly increased in SHR as compared to the non-stressed SHR (11.03 +/- 0.81 and 11.36 +/- 0.33 nmol/g tissue, respectively). In WKY rats, the PU level was significantly increased by acute stress in frontal cortex (11.68 +/- 1.12 nmol/g tissue) as compared to the non-stressed WKY (6.90 +/- 1.44 nmol/g tissue). After chronic stress, the PU levels in frontal cortex and hippocampus of SHR (12.44 +/- 0.54 and 11.34 +/- 0.66 nmol/g tissue, respectively) significantly decreased as compared to acute-stressed groups (15.99 +/- 0.45 and 14.01 +/- 0.95 nmol/g tissue, respectively). In WKY rats, after chronic stress, the PU level was significantly decreased in frontal cortex (5.73 +/- 0.36 nmol/g tissue) as compared to acute-stressed groups (11.68 +/- 1.12 nmol/g tissue). The PU levels in frontal cortex and hippocampus of acute-stressed (15.99 +/- 0.45 nmol/g tissue and 14.10 +/- 0.95 nmol/g tissue, respectively) and chronic-stressed (12.44 +/- 0.54 and 11.34 +/- 0.66 nmol/g tissue, respectively) SHR were significantly higher than acute-stressed (11.68 +/- 1.12 and 9.76 +/- 0.45 nmol/g tissue, respectively) and chronic-stressed (5.73 +/- 0.36 and 8.44 +/- 0.71 nmol/g tissue, respectively) WKY rats. The present study provides the higher basal PU level and stress-induced PU response in SHR as compared to WKY rats may be related to enhanced response of hypothalamic-pituitary-adrenocortical axis and sympathetic influence that may significantly contribute to the development of hypertension in SHR.     

Effects of vascular constriction on occlusive thrombus formation of rat mesenteric artery

Effects of vascular constriction on thrombotic occlusion was evaluated using rat mesenteric arteries and video-recording system attached to the microscope. Topical application of norepinephrine of 1, 10 and 100 micrograms/ml reduced the arterial diameter dose dependently from 297 +/- 41 mu to 166 +/- 50, 87 +/- 18 and 84 +/- 11 mu (mean +/- SD, n = 7), respectively. The diameter reduction by the higher 2 doses persisted for more than 30 minutes until the wash out of the agent. But, no thrombus formation was observed. A reproducible thrombus formation was induced by inserting a glass micropipette into the vascular lumen. The maximal percent occlusion by the thrombus was 80 +/- 11% (range; 67 to 95%, n = 7). The topical application of 10 micrograms/ml norepinephrine induced vasoconstriction and increased the percent occlusion significantly to 97 +/- 8% (p less than 0.05). Complete occlusion of the lumen developed in 6 of 7 rats after the agent and in 2 rats it was not released until the wash out of the agent for more than 30 minutes. Thrombus formation itself did not change the arterial diameter at the site of thrombus formation as well as at sites of 300 and 600 mu down stream. It is suggested that the vascular constriction alone does not necessarily cause thrombus formation but may aggravate the arterial flow reduction induced by thrombosis.     

Normalization of endothelial and inducible nitric oxide synthase expression in brain microvessels of spontaneously hypertensive rats by angiotensin II AT1 receptor inhibition.

Inhibition of angiotensin II AT1 receptors protects against stroke, reducing the cerebral blood flow decrease in the periphery of the ischemic lesion. To clarify the mechanism, spontaneously hypertensive rats (SHR) and normotensive control Wistar Kyoto (WKY) rats were pretreated with the AT1 receptor antagonist candesartan (0.3 mg. kg.(-1) d(-1)) for 28 days, a treatment identical to that which protected SHR from brain ischemia, and the authors studied middle cerebral artery (MCA) and common carotid morphology, endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) messenger RNA (mRNA), and protein expression in cerebral microvessels, principal arteries of the Willis polygon, and common carotid artery. The MCA and common carotid artery of SHR exhibited inward eutrophic remodeling, with decreased lumen diameter and increased media thickness when compared with WKY rats. In addition, there was decreased eNOS and increased iNOS protein and mRNA in common carotid artery, circle of Willis, and brain microvessels of SHR when compared with WKY rats. Both remodeling and alterations in eNOS and iNOS expression in SHR were completely reversed by long-term AT1 receptor inhibition. The hemodynamic, morphologic, and biochemical alterations in hypertension associated with increased vulnerability to brain ischemia are fully reversed by AT1 receptor blockade, indicating that AT1 receptor activation is crucial for the maintenance of the pathologic alterations in cerebrovascular circulation during hypertension, and that their blockade may be of therapeutic advantage.     

Genetic hypertension and increased susceptibility to cerebral ischemia.

A review of the sensitivity of genetically hypertensive rats to cerebral ischemia was presented together with original data describing the systematic comparison of the effects of focal ischemia (permanent and temporary with reperfusion) performed in hypertensive and normotensive rats (i.e., blood pressures verified in conscious instrumented rats). Microsurgical techniques were used to isolate and occlude the middle cerebral artery (MCAO) of spontaneously hypertensive (SHR), Sprague-Dawley (SD) and Wistar Kyoto (WKY) rats at the level of the inferior cerebral vein. Following permanent (24 h) MCAO, persistent and similar decreases in local microvascular perfusion (i.e., to 15.6 +/- 1.7% of pre-MCAO levels) were verified in the primary ischemic zone of the cortex for all strains using Laser-Doppler flowmetry. A contralateral hemiplegia that occurred following MCAO, evidenced by forelimb flexion and muscle weakness, was greater in SHR (neurological grade = 2.0 +/- 0.1) than SD (1.0 +/- 0.4) or WKY (0.7 +/- 0.4) rats (N = 7-9, p less than 0.05). SHR also exhibited sensory motor deficits following MCAO compared to sham-operation, with decreased normal placement response of the hindlimb (% normal = 20 vs. 83, N = 23-30, p decreased rota-rod (41 +/- 7 vs. 126 +/- 19 on rod, N = 10-15, p less than 0.05) and balance beam (25 +/- 5 vs. 116 +/- 29 s on beam, N = 5-7, p less than 0.05) performance. However, an index of general motor activity was not affected by permanent MCAO. Triphenyltetrazolium-stained forebrain tissue analyzed by planimetry revealed a significantly larger and more consistent cortical infarction in SHR (hemispheric infarction = 27.9 +/- 1.5%) compared to SD (15.4 +/- 4.1%) and WKY (4.0 +/- 2.4%) rats (N = 7-9, p less than 0.05), occupying predominantly the frontal and parietal areas. Also, a significant degree of ipsilateral hemispheric swelling (4.6 +/- 0.9%, N = 7-9, p less than 0.05) and increased brain water content (78.4 +/- 0.3% to 80.4 +/- 0.2%, N = 8-9, p less than 0.05) was identified in SHR that was not observed in SD or WKY rats. A novel model of temporary MCAO also was evaluated in the hypertensive and normotensive rat strains. Initially, the effect of increasing MCAO-time followed by 24 h reperfusion in SHR was studied. During temporary MCAO (20 to 300 min), persistent and stable decreases in local microvascular perfusion (i.e., to 15-20% of pre-MCAO levels) were verified in the primary ischemic zones of the cortex.(ABSTRACT TRUNCATED AT 400 WORDS)     

The blood-brain barrier in young spontaneously hypertensive rats

It has been shown that the blood-brain barrier (BBB) of chronically hypertensive adult spontaneously hypertensive rats (SHR) is less susceptible to disruption during acute superimposed hypertension than normotensive controls. The purpose of this study was to determine if the BBB of young SHR, not yet markedly hypertensive, was similarly protected during superimposed acute hypertension. Spontaneously hypertensive rats (n = 22) and normotensive Wistar-Kyoto rats (WKY) (n = 23) 4–5 weeks of age were anesthetized with secobarbital sodium (50 mg/kg) intraperitoneally and acute hypertension was produced by an intravenous injection of norepinephrine (75 μg). Permeability of the BBB was studied with radioactive iodine serum albumin (RISA) injected intravenously. The ratio of brain-to-blood RISA × 100 was used as an index of permeability of the BBB expressed as % protein transfer. In WKY exposed to acute hypertension mean arterial pressure increased by 52 ± 2 mmHg and in SHR the increase was 49 ± 3 mmHg. The protein transfer of the cerebral hemispheres was 1.17 ± 0.30% in WKY and 0.90 ± 0.20% in SHR ( P < 0.40). These data indicate that BBB protein transfer during acute superimposed hypertension does not differ between young SHR and WKY. Thus, the reduced susceptibility to BBB disruption in chronically hypertensive adult SHR is not present in young SHR, making them as susceptible as WKY to cerebral complications related to protein transfer during acute hypertension.     

Mortality and histological findings of the brain during and after cerebral ischemia in male and female spontaneously hypertensive rats

Mortality and pathological changes of the brain during and after cerebral ischemia induced by bilateral carotid artery occlusion (BCO) were studied in male and female spontaneously hypertensive rats (SHR). Systolic arterial blood pressure at rest was significantly higher in male SHR (228 +/- 13 mm Hg, mean +/- S.E.M.) than female (192 +/- 12) (P less than 0.05). The average survival time during permanent occlusion was 11 +/- 6 h (mean +/- S.D.) in male SHR and 17 +/- 7 in female (P less than 0.005), though the cumulative mortality during 24-h ischemia was not different between male (88%) and female SHR (84%). Severe ischemic changes of nerve cells in the brain, especially in the cortex and hippocampus, were observed in 50% of male SHR at 3-h ischemia, while only 15% was observed in female SHR even after 7-h ischemia. After the temporary ischemia followed by reperfusion for 24 h, the mortality was varied between male and female SHR; 0, 31 and 100% after 1-, 3- and 5-h ischemia, respectively, in male SHR and 0% after 1- to 3-h ischemia and 33% after 5- to 7-h ischemia, respectively, in female. Ischemic changes of the brain tissue, such as acidophilic cytoplasm, nuclear degeneration and intercellular edema, were more frequent and severe in male SHR than female after recirculation following 3- or 5-h ischemia. It is concluded that the mortality and post-ischemic viability seem to be determined by the duration of ischemia and also by the degree of the neuronal damage, and female SHR is more tolerated for ischemic insult in comparison to male SHR.     

Electrophysiological properties of neurons in the rostral ventrolateral medulla of normotensive and spontaneously hypertensive rats

Single unit activities were recorded from the rostral ventrolateral medulla (RVL) of pentobarbital-anesthetized normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Throughout the recording period, arterial blood pressures of WKY (mean arterial pressure, MAP = 103.1 mm Hg) and SHR (MAP = 159.2 mm Hg) remained stable at the respective basal levels. The units recorded in this study were all spontaneously active and cardiac-locked. Two types of discharge patterns, namely single and double discharges, were identified. These single and double discharge units were found to distribute randomly in RVL. In WKY, 92.6% of RVL neurons exhibited single discharges whereas in SHR, the majority (57%) of RVL neurons exhibited double discharges. The mean firing rate of single discharge units in RVL of SHR was significantly higher than that of WKY, whereas the mean firing rate of double discharge units in WKY was similar to that of SHR. About half of the units studied were also tested for antidromic collision; all units tested could be antidromically activated from the intermediolateral column (IML) of the thoracic spinal cord and the lowest threshold sites were consistently localized within IML. In both groups of rats, the axonal conduction velocity of RVL neurons showed a bimodal distribution viz. the fast and slow conducting axons. The mean conduction velocities of each of these two groups of neurons in WKY and SHR were similar. Most of the double discharge units in WKY and SHR belonged to the fast conducting type.(ABSTRACT TRUNCATED AT 250 WORDS)