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Biomedical subjects

S B Gertner

Publications and source records attributed to S B Gertner.

At least 19 recordsLinked to original sources
PubMed1996

Hemodynamic profile of activation of histamine H3 receptors by R-alpha-methylhistamine in the guinea pig.

1. The effect of R-alpha-methylhistamine, a histamine H1 receptor agonist, was studied on cardiovascular hemodynamics in bilateral vagotomized, anesthetized guinea pigs. 2. R-alpha-methylhistamine (100 micrograms/kg, IV) a dose that selectively activates histamine H3 receptors, produced hypotension and bradycardia. Total peripheral resistance (TPR) and rate pressure product (RPP) were also decreased at this dose. 3. Pretreatment with the ganglionic blocker hexamethonium (20 mg/kg, IV) blocked the blood pressure (BP), heart rate (HR), TPR, and RPP effects of R-alpha-methylhistamine (100 micrograms/kg, IV). Hexamethonium did not block the hypotensive and TPR lowering actions of the muscarinic agonist methacholine (1 and 3 micrograms/kg, IV). 4. Pretreatment with the alpha 1-adrenoceptor antagonist prazosin (0.5 mg/kg IV), blocked R-alpha-methylhistamine's (100 micrograms/kg, IV) effects on BP, TPR, and RPP. Prazosin did not antagonize the bradycardia effect of R-alpha-methylhistamine. 5. Pretreatment with the beta-adrenoceptor antagonist atenolol (1 mg/kg, IV) did not alter the BP, TPR, or RPP actions of R-alpha-methylhistamine. The HR effects of R-alpha-methylhistamine were blocked by atenolol. 6. The hemodynamic effects of R-alpha-methylhistamine were compared to the hemodynamic profile of the calcium channel blocker, verapamil (0.5 mg/kg, IV). Verapamil had little effect on TRP and had a greater cardiac depressant effect as evidenced by a significant reduction in HR and cardiac output (CO). 7. In summary, these results show that activation of prejunctional H3 receptors with R-alpha-methylhistamine decreases basal, BP, HR, TPR, and RPP in anesthetized guinea pigs. The fall in BP is mediated by a decrease in TPR. Furthermore, the inhibitory effects of R-alpha-methylhistamine on sympathetic control of the vasculature appears to impart a greater physiologic effect on the H3-histamine mediated hypotension than its inhibitory effects on sympathetic agents to the heart.

Animals↗
PubMed1995

Vagal stimulation augments pulmonary anaphylaxis in the guinea pig lung.

The effect of bilateral vagal stimulation on aerosolized antigen-induced responses was examined in the sensitized, perfused guinea pig lung. Vagal stimulation in the sensitized, perfused lung resulted in bronchoconstriction (peak response 160 +/- 18% above baseline) that was unaffected by either atropine (1 microM), a muscarinic receptor antagonist, or CP 96,345 (1 microM), a NK-1 receptor antagonist, but was transiently augmented in the presence of physostigmine (1 microM), a cholinesterase inhibitor, through an atropine-sensitive mechanism. However, SR 48968 (1 microM), a NK-2 receptor antagonist, and SR 48968 + CP 96,345 reduced by approximately 50 and 90%, respectively, vagally mediated increases in intratracheal pressure in the perfused lung. Simultaneous challenge with vagal stimulation and aerosolized antigen in the sensitized perfused lung resulted in a significant (p < 0.01) increase in intratracheal pressure (Pi), pulmonary arterial pressure (Ppa), and lung weight (LW) compared with either vagal stimulation or aerosolized antigen alone. Increases in Pi, Ppa, and LW in response to vagal stimulation + aerosolized antigen were associated with elevated venous effluent concentrations of thromboxane A2 (TXA2), prostacyclin, leukotriene C4, and histamine. Vagally mediated potentiation of aerosolized antigen-induced increases in Pi, Ppa, and LW was unaffected by atropine or CP 96,345 but was inhibited by the NK-2 receptor antagonist, SR 48968. These data suggest that vagally mediated (predominantly NK-2) potentiation of aerosolized antigen-induced increases in Pi, Ppa, and LW is characterized by elevated venous effluent concentrations of eicosanoids and histamine.

Anaphylaxis↗
PubMed1994

Species differences in the cardiovascular responses to histamine H3 receptor activation.

Potential species differences in cardiovascular responses to histamine H3 receptor activation were studied in the conscious guinea pig, rabbit, normotensive rat and the spontaneously hypertensive rat. R-alpha-Methylhistamine (100 micrograms/kg i.v.) decreased blood pressure in both the guinea pig and the rabbit. In the guinea pig, R-alpha-methylhistamine decreased heart rate, whereas in the rabbit it produced a tachycardia. In the normotensive rat and spontaneously hypertensive rat, R-alpha-methylhistamine (100 micrograms/kg i.v.) had no effect on blood pressure and heart rate. The cardiovascular action of R-alpha-methylhistamine in the guinea pig and rabbit was blocked by pretreatment with thioperamide (1.0 mg/kg i.v.) but not by chlorpheniramine (0.3 mg/kg i.v.) or cimetidine (3.0 mg/kg i.v.), respectively. These results indicate species differences in cardiovascular responses to histamine H3 receptor activation.

Animals↗
PubMed1993

Production by R-alpha-methylhistamine of a histamine H3 receptor-mediated decrease in basal vascular resistance in guinea-pigs.

1. The effect of the selective histamine H3 receptor agonist, R-alpha-methylhistamine given intravenously (10-100 micrograms kg-1) was examined on baseline total peripheral resistance (TPR), and cardiovascular haemodynamics in bilaterally vagotomized, anaesthetized guinea-pigs. 2. R-alpha-methylhistamine produced a dose-dependent hypotension and fall in TPR at 30 and 100 micrograms kg-1. A decrease in heart rate (HR) was observed at a dose of 100 micrograms kg-1. R-alpha-methylhistamine (10-100 micrograms kg-1) also produced a dose-dependent fall in rate pressure product (RPP). There was no effect on cardiac output (CO) or stroke volume (SV) at these doses. 3. Histamine H1 and H2 blockade in animals pretreated with a combination of chlorpheniramine (0.3 mg kg-1) and cimetidine (3.0 mg kg-1) did not alter the haemodynamic actions of R-alpha-methyl-histamine (100 micrograms kg-1, i.v.). Pretreatment with the selective H3 antagonist, thioperamide (1 mg kg-1), completely blocked the action of R-alpha-methylhistamine on haemodynamic parameters. 4. To study the mechanism of action of R-alpha-methylhistamine, the vasodilator hydralazine (1 mg kg-1, i.v.) was used. Hydralazine lowered BP, TRP and RPP in guinea-pigs pretreated with ipratropium (50 micrograms kg-1, i.v.). Hydralazine had no effect on HR, SV or CO. 5. R-alpha-methylhistamine (100 micrograms kg-1) did not affect the vasopressor action and increases in TPR produced by adrenaline (1 and 3 micrograms kg-1). On the other hand, the vasodilator hydralazine (1 mg kg-1, i.v.) inhibited the effects of adrenaline (3 micrograms kg-1) on TPR and RPP. The effect of both doses of adrenaline on BP were attenuated by hydralazine. Therefore, the inhibitory effects of R-alpha-methylhistamine are not mediated through a direct action on vascular smooth muscle.6. In adrenalectomized guinea-pigs, R-alpha-methylhistamine (100 microg kg-1) produced a drop in BP and HR.There was no difference between the effects of R-alpha-methylhistamine on blood pressure and heart rate in adrenalectomized and non-adrenalectomized guinea-pigs.7. These results show that activation of peripheral H3 receptors lowers basal BP, HR and TPR, most likely by a peripheral prejunctional mechanism. The fall in BP and TPR is probably due to a decrease in noradrenaline release from sympathetic effector nerves innervating the resistance blood vessels.

Adrenalectomy↗
PubMed1992

Dietary calcium modifies concentrations of lead and other metals and renal calbindin in rats.

We studied the effects of dietary calcium on kidney, femur, testis, liver, heart and brain concentrations of lead, magnesium, iron, copper, calcium and zinc in rats exposed to lead for 1 y. Renal levels of the 28,000 Da, vitamin D-dependent, calcium-binding protein calbindin-D28K were also measured. Seventy-two weanling male Sprague-Dawley rats were randomly assigned to one of nine treatment groups. Rats were fed diets containing 0.1, 0.5 or 2.5% Ca for 52 wk and were simultaneously given either 0, 50 or 100 mg lead/L in their drinking water. Rats fed the 0.1% Ca diet had organ lead concentrations that were two- to 20-fold greater than the corresponding animals fed 0.5% Ca. Rats fed diets containing 2.5% Ca had the lowest organ lead concentrations. Despite substantial effects of diet Ca on organ lead concentrations, Ca did not significantly influence concentrations of most other divalent metals studied with the exception of kidney calcium and magnesium, testis iron, plasma ionic calcium and magnesium, and several femur metals. Kidney calcium concentrations were lower in rats fed 2.5% Ca diets than in those fed 0.1 or 0.5% Ca diets. For rats not given lead, renal calbindin concentrations were highest in rats fed 0.1% Ca, and lowest in rats fed 2.5% Ca. Lead inhibited an increase in renal calbindin in the rats fed 0.1% Ca, but paradoxically increased renal calbindin levels in animals fed 2.5% Ca.

Administration, Oral↗
PubMed1991

Dietary lead and calcium: effects on blood pressure and renal neoplasia in Wistar rats.

We examined the potential of increased Ca in the diet to modify the effects of Pb on tissue metal concentrations, blood pressure and the incidence of renal tumours. We randomly assigned 48, 5-wk-old male Wistar rats to one of six treatment groups. They were fed a low (0.2%) or high (4.0%) Ca diet for 31 wk and given 0, 1.0 or 100 micrograms Pb/mL in drinking water. In the low Ca groups, increasing concentrations of Pb produced graded increases in mean blood pressure. Rats receiving 4.0% Ca had higher mean blood pressures than the animals fed the 0.2% Ca diet. The 4.0% Ca diet also caused renal and urinary bladder stones to develop in some rats. The high Ca diet did not prevent dose-dependent increases in tissue Pb accumulation, but it caused significant decreases in kidney Cu, femur Mg and Fe in kidney, liver and testis. Femur Mg and Fe and liver Fe concentrations were lowest in rats receiving 4.0% Ca and 100 micrograms Pb/mL. Precancerous and cancerous renal lesions occurred to the greatest extent in the rats receiving 100 micrograms Pb/mL and the high Ca diet. These results suggest that high dietary Ca does not protect against Pb-induced increases in blood pressure or Pb accumulation in tissues and may often produce nephrocalcinosis. In addition, high dietary Ca in the presence of Pb may increase the incidence of renal tumors.

Animals↗
PubMed1990

Central cardiovascular responses of histamine and homodimaprit in normal and hypophysectomized rats.

Central administration of histamine in conscious rats produced half the pressor response in hypophysectomized rats compared to normal animals. The pressor response was blocked completely by hexamethonium in hypophysectomized rats but not at all in normal rats. Homodimaprit given centrally, gave pressor effects of equal magnitude in both groups. In normal rats, it caused significantly higher blood blood pressure following ganglionic blockade, whereas in hypophysectomized rats hexamethonium did not block the response to homodimaprit. These results, plus previous findings, show that histamine, given centrally, raises blood pressure in normal conscious animals by releasing vasoactive substances from the brain. In hypophysectomized rats it stimulates sympathetic output. Homodimaprit, on the other hand, produces its pressor action by the release of vasoactive substances from the brain both in normal and hypophysectomized animals. A hypothesis is proposed to suggest that parallel neuronal processing occurs in the brain when histamine is given.

Animals↗
PubMed1990

Unexpected changes in urinary catecholamines and vanillylmandelic acid following rape assault.

Although psychological changes are recognized to occur in rape assault survivors there is no information on the biochemical changes in these victims. This study compares urinary catecholamines and metabolites in 17 rape victims to two female control groups (one of which engaged in normal sexual intercourse and the other did not). We found, in the rape victims, unexpected changes in the excretion pattern of catecholamines and metabolites as compared to the various control groups. The most significant difference was the dramatic increase in urinary conjugated dopamine (P less than 0.01) in the rape victims which remained elevated for over 24 hr. Urinary vanillylmandelic acid (VMA) rose significantly in rape assault victims when compared to the normal control group. The VMA levels in rape victims were significantly lower, however, than in the women who had undergone (normal) sexual intercourse (P less than 0.01). Urinary free epinephrine showed a marked decline and remained depressed for over 24 hr in the rape assault victims (P less than 0.01) compared to normal controls. Some possible reasons for these patterns in catecholamines and metabolite excretion are suggested. These changes may be of importance in the poststress syndrome that occurs following the rape assault. In summary, a different profile of catecholamine and metabolite excretion patterns was found in rape compared to normal sexual intercourse. The enhanced dopamine excretion is contrary to the expected change of enhanced epinephrine secretion in severe stress.

Adult↗
PubMed1989

Measurements of postcoital sympathetic activity in females by means of vanillylmandelic acid.

Urinary vanillylmandelic acid (VMA), the final metabolite of epinephrine and norepinephrine, and creatinine (Cr) were measured 1 hr before, within an hour after intercourse, and in a 23-hr pooled sample after intercourse in 11 females. The results were compared to a group of 8 normal females who abstained from intercourse. The control VMA/creatinine ratios were significantly lower than the preintercourse values (P less than 0.01) as well as the postintercourse and 23-hr pooled postintercourse sample. This ratio, 1 hr postintercourse increased significantly (P less than 0.01) over the preintercourse values. The pooled 23-hr postintercourse sample remained high and was significantly different from preintercourse but not from the postintercourse sample. The absolute values of VMA showed relatively similar significance. This study provides objective evidence in the female for the considerable involvement of the sympathetic system during sexual intercourse. In addition, it shows that the group that was planning to have sexual intercourse, 1 hr prior to intercourse, already had VMA/creatinine ratios double over the control group. Such objective information has hitherto not been available.

Adult↗
PubMed1989

Studies on the cardiovascular actions of central histamine H1 and H2 receptors.

Histamine administered i.c.v. to conscious freely moving rats results in dose-related pressor responses and bradycardia. The selective H1 agonist pyridylethylamine (PEA) and the H2 agonist impromidine (IMP) were utilized to characterize the central receptor subtypes involved in the central cardiovascular actions of histamine. Blood pressure and heart rate were monitored directly via indwelling carotid catheters, and drugs were administered i.c.v. through permanently implanted cannulas. Central administration of PEA or IMP produced dose-dependent pressor responses and bradycardia. The H1 antagonist chlorpheniramine blocked the pressor response, but not the bradycardia produced by PEA. In contrast, the H2 antagonist BMY-25405 blocked both the increase in blood pressure and the bradycardia induced by IMP. Crossover experiments were carried out to examine the specificity of the antagonists' actions. Chlorpheniramine failed to block the actions of IMP and BMY-25405 likewise was ineffective in blocking the actions of PEA. These results suggest that both central H1 and H2 receptors mediate the central pressor effects of histamine, and that PEA and IMP are selectively acting at their respective receptors in the brain. The heart rate effects appear to be mediated directly by central H2 actions, as BMY-25405 was capable of blocking the heart rate changes. The finding that IMP is less potent in the central nervous system, compared to its known greater potency in the periphery, suggests that peripheral and central H2 receptors may be pharmacologically distinct.

Animals↗
PubMed1987

Effects of centrally administered H2 antagonists on motor activity.

Two structurally distinct H2 antagonists, cimetidine and BMY 25,368, were injected into the cerebral ventricles of mice. Both drugs produced reductions in locomotor activity and rotorod latencies. The effects of the H2 antagonists on locomotor activity were attenuated by the H2 agonist, impromidine, as well as by the H1 antagonist, chlorpheniramine. When given alone, chlorpheniramine had no effect on locomotor activity, while impromidine reduced locomotion. These data suggest that histaminergic receptors may mediate important actions on arousal and sedation mechanisms.

Animals↗
PubMed1987

Elevated creatinine levels in rape assault survivors.

Urine specimens were collected from alleged rape survivors. In 13 of the 29 survivors, creatinine levels were over 150 mg/dl, and nine of these were over 200 mg/dl. These elevated urine creatinine levels persisted for some time after the alleged rape attacks. Various controls yielded overall levels below those of the alleged rape assault survivors. When control values of creatinine and osmolality of pre- and postintercourse samples were plotted and compared by linear regression covariance analysis to the data on alleged rape survivors, the levels of urinary creatinine in the alleged rape survivors were higher than would have been expected from urine osmolality increases. The dissimilarity of the two sets of data has a p value less than 0.0001. These findings might serve as supplemental objective evidence of rape (or terror) that could be used medicolegally.

Adolescent↗
PubMed1986

Effects of centrally administered H2 antagonists in the behavioral despair test.

Injection of the histamine-2 (H2) receptor antagonist cimetidine into the lateral ventricles of mice produced a dose-related reduction in swimming in the behavioral despair test. This response can be attenuated by intracerebroventricular (ICV) injection of the histamine-1 (H1) receptor antagonist chlorpheniramine, or the H2 receptor agonist impromidine, given simultaneously with cimetidine. At doses which blocked cimetidine, neither chlorpheniramine nor impromidine alone had effects on swimming. A similar decrease in swimming behavior was also seen after ICV injections of the non-imidazole H2 antagonist, BMY 25,368. This effect of BMY 25,368 was also attenuated by chlorpheniramine and impromidine. These results suggest that H1 and H2 receptors in the brain may mediate opposing behavioral effects.

Animals↗
PubMed1986

Studies on the desensitization of the central cardiovascular responses of histamine.

Intraventricular administration of histamine (HA) in conscious freely moving rats produces a dose-dependent pressor response and bradycardia. These responses are diminished profoundly when a second injection of HA is given within a short time after the first injection. In this study, the specific HA H1 agonist, pyridylethylamine, and the specific H2 agonist, impromidine, were used to examine the nature of this tachyphylaxis. Blood pressure and heart rate were measured directly from indwelling carotid catheters, and drugs were administered in three consecutive intraventricular injections to conscious freely moving rats at 30-min intervals. HA, the H2 agonist, impromidine and the combined injection of pyridylethylamine and impromidine induced tachyphylaxis of the pressor response. The H1 agonist, pyridylethylamine and the HA-N-methyltransferase inhibitor, SKF-91488 (homodimaprit) did not show tachyphylaxis. Heart rate responses were more complex and only HA demonstrated tachyphylaxis of the bradycardia. It is concluded that the tachyphylaxis of the pressor response caused by repeated injections of HA results from the desensitization of central HA H2 receptors.

Animals↗
PubMed1984

The effect of intrahypothalamic injection of homodimaprit on blood pressure.

Bilateral injection of the inhibitor of histamine-N-methyltransferase, SKF 91488, which is also known as homodimaprit (5 micrograms), into the preoptic area of the rat produced delayed hypertension, tachycardia and hyperthermia. Some animals exhibited pulmonary edema. These effects were only noted 18-24 hr after an injection and were not an artifact of the injection, since the administration of artificial cerebrospinal fluid produced none of these effects. At the time noted, lesions of the rostral hypothalamus, including the preoptic area, were evident. Injection of a vasopressin antagonist, intravenously, did not lower the blood pressure of the hypertensive animals nor did previous bilateral adrenal demullation prevent or delay the hypertension or tachycardia. Therefore, it does not appear that hypersecretion of either vasopressin or adrenal catecholamines contributed to the cardiovascular effects. Peripheral pretreatment with the sympathetic neurotoxin 6-hydroxydopamine however, did prevent the delayed rise in blood pressure following an injection of homodimaprit. From these studies, it is concluded that the injection of homodimaprit produces lesions in the preoptic area, resulting in hypertension that is maintained by excessive activation of the sympathetic nervous system.

Adrenal Medulla↗
PubMed1983

Studies on the mechanism of the cardiovascular action of central injections of histamine.

The role of the sympathetic nervous system in the mediation of cardiovascular function, following administration of histamine centrally was investigated. Intracerebroventricular (i.c.v.) injections of histamine into the lateral ventricle of conscious rats caused a dose-dependent increase in blood pressure as well as a dose-dependent fall in heart rate. The pressure and heart rate responses were both attenuated by pretreatment with chlorpheniramine. Peripheral blockade of autonomic ganglia with hexamethonium failed to block the centrally-mediated pressor response to histamine. Peripheral chemical sympathectomy with 6-hydroxydopamine also did not inhibit the pressor response to histamine. In this latter group of animals the pressor response to histamine was potentiated. It is concluded that in the conscious rat, increased in blood pressure resulting from central stimulation with histamine are not mediated solely through the activation of the sympathetic nervous system and are, at least in part, due to the release of a vasopressor substance.

Animals↗
PubMed1983

The effect of a vasopressin antagonist on the pressor response to histamine administered centrally.

The mechanism for the pressor response to intracerebroventricularly (i.c.v.) administered histamine was studied. Histamine (HA), when injected intracerebroventricularly in rats, produced a dose-dependent increase in mean arterial pressure (MAP) which was subject to tachyphylaxis. Spinal transection at C-7 in the anesthetized rat did not attenuate the rise in blood pressure. The possibility that the release of 8-arginine vasopressin was responsible for the rise in blood pressure was explored. By pretreating conscious freely-moving rats with a specific antagonist to the vasopressor action of vasopressin viz., [1-beta-mercapto-beta, beta-cyclopentamethyleneproprionic acid), 2-(O-methyl) tyrosine] arginine-vasopressin, there was a statistically-significant attenuation of the pressor response to intracerebroventricularly administered histamine. The antagonist however, did not totally abolish the pressor response, regardless of the dose employed. Concomitant administration of hexamethonium and the vasopressin antagonist did not further attenuate the response. Previous adrenal demedullation did not diminish the response to intracerebroventricularly administered histamine, nor was there any evidence for release of angiotensin II since pretreatment with saralasin did not attenuate the cardiovascular response. These findings suggest that vasopressin along with other as yet undefined substances, are released from the central nervous system to produce the increase in blood pressure after intracerebroventricularly administered histamine.

Angiotensin II↗