Ketanserin versus urapidil: age-related cardiovascular effects in conscious rats.

To examine whether serotonin (5-hydroxtryptamine, 5-HT)-mediated mechanisms for regulating blood pressure are influenced by advancing age, the cardiovascular effects of ketanserin and urapidil were compared in two groups of conscious rats at ages 4 (young) and 24 (old) months. Old rats had higher mean pressures but the same basal heart rates as young rats prior to drug treatment. Subsequent treatment with either ketanserin or urapidil produced similar cardiovascular effects.

Abated cardiovascular responses to chronic oral lisinopril treatment in conscious elderly rats.

To determine whether the cardiovascular effects of chronic treatment with lisinopril are age related, we compared baroreflex sensitivity and pressor responsiveness in 4-mo- and 21-mo-old male rats that had been given oral lisinopril daily for 4 wk. Reflex bradycardia elicited by elevating blood pressure with phenylephrine was stronger in 4-mo-old rats than it was in 21-mo-old rats and also stronger in lisinopril-treated rats than it was in untreated rats of the same age. Pressor responses to angiotensin or norepinephrine were recorded after combined cholinergic and beta-adrenergic blockade and then analyzed not only as absolute but also as percent increases in mean pressure.

Does chronic ketanserin treatment enhance bradycardia in old rats by serotonergic blockade?

To determine if the cardiovascular effects of chronic treatment with ketanserin would vary with increasing age, ketanserin was given by daily gavage for 14 days to male Sprague-Dawley rats at ages 4, 14, or 24 months. Before treatment, 24-month-old rats had higher blood pressures and weaker reflex heart rate responses than younger rats. Treatment with ketanserin caused hypotension, enhanced bradycardia, attenuated reflex tachycardia, and reversed serotonin (5-HT) responses, with all effects being more pronounced in 24-month-old rats than in younger rats.

Short-term lisinopril treatment in old rats worsens impairment of angiotensin-induced reflex bradycardia.

To determine how short-term treatment with an angiotensin-converting enzyme (ACE) inhibitor affects drug-induced reflex bradycardia at different ages in conscious rats, we compared the magnitude of drug-induced reflex bradycardia before and after injecting bolus intravenous doses of lisinopril, 1 mg/100 g, in male Sprague-Dawley rats aged 4 (young) or 19 (old) months. Anesthetic artifacts were avoided by recording all drug-induced cardiovascular responses from femoral arterial cannulas implanted 1 week earlier. For eliciting reflex bradycardia, blood pressure was increased by graded intravenous infusion of angiotensin or phenylephrine.

Conscious obese rats have impaired reflex bradycardia and enhanced norepinephrine sensitivity.

Male Sprague-Dawley rats fed a condensed milk diet were classified as either "obesity susceptible" (OS) or "obesity resistant" (OR) based on body weight increases attained after 12 wk. Overall caloric intake in OS rats was higher than in chow-fed controls, and OS rats were heavier than chow-fed controls or OR rats. There were no significant differences in blood glucose, serum insulin, ventricular weight, basal blood pressure, or heart rate.

Hypotensive and reflex bradycardic effects of ketanserin, but not of prazosin, enhanced selectively in aging conscious rats.

To determine whether cardiovascular effects of ketanserin are altered differently with aging as compared with those of prazosin, we recorded blood pressure (BP) and heart rate (HR) changes produced by treatment with either drug in three age groups of conscious Sprague-Dawley rats. BP was decreased more by ketanserin in 24-month than in 4- or 14-month-old rats, but was decreased equally by prazosin in all age groups. Pressor responses to phenylephrine (PE) were consistently abolished by both drugs, indicating that the greater hypotensive effects of ketanserin in 24-month-old rats were not due simply to alpha 1-adrenergic blockade.

Contrasting baroreflex effects of muscimol versus bicuculline injected into the nucleus tractus solitarius in anesthetized rats.

To examine how the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) affects baroreflex regulation, reflex heart rate and renal nerve responses were recorded in anesthetized rats after bilateral injections of muscimol or bicuculline into the nucleus tractus solitarius (NTS). Blood pressure, heart rate, and renal nerve activity were increased by the GABA agonist muscimol and decreased by the GABA antagonist bicuculline. Control injections of the vehicle alone were ineffective.

Surgical "touch artefacts" of the cerebral cortex. An experimental study with light and electron microscopic analysis.

In surgically excised brain tissue a very common artefact, unrelated to the presence or absence of a genuine pathological process, involves the water content of cortical neurons. Nerve cells may show massive watery swelling of both their cytoplasm and nuclei or conversely may become shrunken and dark-staining. The most important aspect of this alteration is that it may lead to mistaken histopathological interpretation, but the question also arises whether such changes, presumably caused by exposure, touch, pressure or the combination of all 3, in the living patient, would persist after surgery and would eventually result in irreversible damage to the involved neurons? Thirty rats were operated in this experiment: craniotomy and opening of the dura mater was done over one convexity and slight pressure (uniformly calibrated for all animals) was applied to the exposed cortex.

Aneurysm of the left middle cerebral artery caused by myxoid degeneration of the vessel wall.

Background: Myxoid degeneration of arterial walls may result in dissection and dissecting aneurysms in extracranial and intracranial portions of cerebral arteries. Rarely, saccular aneurysms may also develop on that basis, but thus far these have only been reported in the cervical portions of the carotid arteries. We describe a case of a nondissecting aneurysm of the left middle cerebral artery caused by myxoid degeneration of the media.

Insulin acts centrally to enhance reflex tachycardia in conscious rats.

Systemic and central insulin treatment for 10 days were compared in conscious rats given insulin either by daily subcutaneous injection or by continuous intracerebroventricular infusion. To measure changes in baroreflex sensitivity, heart rate responses elicited reflexly by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside were recorded before and after insulin treatment. Although reflex bradycardia and basal mean pressures and heart rates were unaffected, reflex tachycardia was consistently more pronounced in rats treated with insulin (whether given systemically or centrally) than in vehicle-treated controls.

Selective enhancement in SHR of hypotension and bradycardia caused by NTS-injected serotonin.

To examine whether serotonergic mechanisms in the nucleus tractus solitarius (NTS) become altered by hypertension, responses to serotonin (5-HT) or L-glutamate injected into the NTS were compared in anesthetized rats. Because isotonic saline had appreciable effects whereas artificial cerebrospinal fluid did not, artificial cerebrospinal fluid was routinely used as the vehicle. Microinjections of 5-HT or L-glutamate always reduced mean pressure, heart rate, and renal nerve activity.

Age-related reduction of reflex bradycardia in conscious rats by catecholaminergic nucleus tractus solitarius lesions.

To determine whether catecholaminergic lesions in the nucleus tractus solitarius (NTS) have age-related baroreflex effects, we compared conscious 3-month- and 14-month-old rats pretreated with either 6-hydroxydopamine (6-OHDA) or vehicle injected into the NTS. Body weights fell immediately in both age groups, but after 2 weeks the weight loss persisted only in 14-month-old rats. Mean pressures and heart rates, though diminished after 3 days, were later elevated slightly in 3-month- but not in 14-month-old rats.

Catecholaminergic nucleus tractus solitarius lesions in anesthetized rats alter baroreflexes differently with age.

To explore whether catecholaminergic lesions produced chemically in the nucleus tractus solitarius (NTS) would alter the baroreflex impairment that normally occurs with age, we compared baroreflex responses in 3- and 14-month-old rats given bilateral microinjections of 6-hydroxydopamine (6-OHDA) or its vehicle into the NTS. After 2 weeks, basal pressures were unaffected but heart rates were lower in 14- than in 3-month-old rats. Sympathetic nerve inhibition elicited reflexly during intravenous infusions of sodium nitroprusside was reduced in 3-month-old rats, but increased in 14-month-old rats.

Baroreflex changes produced by serotonergic or catecholaminergic lesions in the rat nucleus tractus solitarius.

To distinguish between catecholaminergic and serotonergic mechanisms for baroreflex regulation in the medulla, we compared rats with chemical lesions produced by injecting 6-hydroxydopamine (6-OHDA) or 5,7-dihydroxytryptamine (5,7-DHT) into the nucleus tractus solitarius (NTS) bilaterally at the caudal tip of the area postrema. After 2 weeks, basal blood pressure and heart rate were unaltered, but blood pressure lability, instead of being increased, was slightly reduced. Baroreflex tests in conscious rats showed that although phenylephrine-induced reflex bradycardia was unaffected, nitroprusside-induced reflex tachycardia was enhanced by 5,7-DHT.

Age-related delay in recovery of beta-adrenergic sensitivity after abrupt propranolol withdrawal in rats.

We compared cardiovascular responses to various adrenergic agonists in conscious 3-month and 12-month old rats that had been treated with propranolol daily for 7 days, to determine whether changes in beta-adrenergic hypersensitivity induced by abrupt propranolol withdrawal would differ with age. Depressor and tachycardic responses elicited by beta-adrenergic stimulation with isoproterenol were still reduced during the first 3 days following propranolol withdrawal, but were restored to pretreatment levels, more slowly in 12-month than in 3-month-old rats. Opposite pressor and bradycardic responses to alpha-adrenergic stimulation with phenylephrine did not differ between age groups, either before or after propranolol withdrawal.

Aging reduces cardiovascular and sympathetic responses to NTS injections of serotonin in rats.

Serotonergic mechanisms for baroreflex modulation could become altered with age. This possibility was explored by comparing cardiovascular and sympathetic effects elicited in 2-month- and 24-month-old rats by injecting serotonin (5-HT) directly into the nucleus tractus solitarius (NTS) which is the primary baroreflex relay station in the medulla. Ensuing decreases in mean pressure, heart rate, and renal nerve firing were significantly smaller in 24-month-old than in 2-month-old rats.

Waning cardiovascular responses to adrenergic drugs in conscious ageing rats.

Blood pressure and heart rate responses to various drugs were recorded in three groups of conscious rats at ages 3-, 12- and 26-months to determine whether cardiovascular responsiveness changes selectively with age. Basal mean pressures were higher while heart rates were lower in 26-month-old rats than in others. Phenylephrine, as an alpha-adrenergic agonist, produced significantly smaller pressor and bradycardic responses in 26-month-old than in younger rats.

Glioblastoma multiforme of the hippocampus in advanced Alzheimer's disease.

An 87-year-old woman suffered from Alzheimer's disease diagnosed 6 years prior to her death. Autopsy showed in addition to far-advanced Alzheimer's disease, a large, partially necrotic glioblastoma occupying her right hippocampus. Occurrence of a glial neoplasm in Alzheimer's disease could well be coincidental, since both entities are fairly common in elderly individuals; it is however, uncommon for gliomas to centre on the hippocampus itself.

Normotensive diabetic BB/W rats show enhanced reflex tachycardia.

Spontaneously diabetic BB/W rats were compared with age-matched regular Wistar and nondiabetic BB/W rats to determine whether the presence of diabetes would alter cardiovascular regulation appreciably. Systolic and mean blood pressures measured with the tail-cuff method from 12 to 26 wk of age tended to be slightly higher in diabetic than nondiabetic BB/W rats, but the differences were not significant. Mean pressures recorded from indwelling catheters in the same rats at 28 wk of age also did not differ significantly, thereby verifying that the diabetic rats were not hypertensive.

Sympathetic activation by chronic insulin treatment in conscious rats.

Normal male Wistar rats pretreated with insulin for 12 days were studied to determine if chronic insulin treatment would reproduce the cardiovascular changes occurring in obese rats with hyperinsulinemia. After 12 days, plasma insulin rose while plasma glucose fell, but basal pressures recorded while the rats were awake remained unchanged. Depressor and tachycardic responses to isoproterenol were enhanced, thereby suggesting that beta adrenergic responsiveness had been increased.

Tissue artefacts caused by sponge in embedding cassettes.

Sponges in embedding cassettes may cause disruptive imprints on the tissues being processed and therefore should not be used in processing tissues. Tissue or lens paper is recommended as a substitute to prevent losing small pieces of tissue through the perforations of the cassette.

Tail-cuff detection of systolic hypertension in different strains of ageing rats.

To identify rat strains suitable for studying age-related development of hypertension we compared pressures measured with the tail-cuff method in different groups of ageing Fischer 344, Wistar, or Sprague-Dawley rats. Preliminary experiments to establish optimal frequency of chronic blood pressure measurement in ageing rats showed that tail-cuff systolic pressures did not differ significantly whether taken weekly or monthly. Repeated tail-cuff measurements were comparable even when a common cuff size was used in different groups of rats with varying tail diameters.

Modification of cardiac ionic currents by photosensitizer-generated reactive oxygen.

The effects of reactive oxygen species (ROS) generated by light and the photosensitizer Rose Bengal on ionic currents in single frog atrial cells were investigated. The excitatory inward sodium and calcium currents were both suppressed by ROS as was the outward, delayed rectifier potassium current. The inactivation kinetics of the sodium current were slowed markedly whereas the kinetics of calcium current inactivation were much less affected and potassium current activation was not changed.

Differential age-dependent attenuation of reflex tachycardia by verapamil in rats.

To determine if verapamil alters baroreflex function differently depending on age, reflex heart rate responses to intravenous infusions of phenylephrine or sodium nitroprusside were compared in conscious 5- and 14-month-old rats before and after daily oral administration of verapamil (100 mg/kg) for 6 days. The effects of verapamil on parasympathetic and sympathetic mediation of heart rate were also assessed by repeating baroreflex tests after treatment with either propranolol or atropine. All reflex heart rate responses were initially smaller in 14- than in 5-month-old rats.

Cardiovascular and sympathetic effects of injecting serotonin into the nucleus tractus solitarius in rats.

Microinjections of serotonin (5-HT) delivered into the nucleus tractus solitarius (NTS) elicit opposite cardiovascular effects depending on the doses used; blood pressure and heart rate are decreased by low doses but increased by high doses. To examine this apparent contradiction, we compared cardiovascular and sympathetic nerve responses elicited in anesthetized rats by using glass micropipettes to inject 5-HT, the vehicle alone or various 5-HT agonists or antagonists into the NTS. Low (0.