Alpha-adrenergic Responsiveness Research Articles

Effect of Orchiectomy on the Alpha Adrenergic Contractile Response of Dog Prostate

Effect of Orchiectomy on the Alpha Adrenergic Contractile Response of Dog Prostate

Beta 3-adrenoceptors and intestinal motility.

Early substantial evidence of the low susceptibility to beta-adrenoceptor antagonists of non alpha-adrenergic responses reducing gut motility and tone was reluctantly accepted as indicating a third beta-receptor subtype different from the beta 1 and beta 2. This applied likewise to lipolysis until new selective "lipolytic" beta-agonists poorly effective at established beta-receptors were introduced. Shortly afterwards these "lipolytic" as well as certain newer and even more selective beta-adrenoceptor agonists were shown to be potent inhibitors of intestinal motility. The latter are the "gut-specific" phenylethanolaminotetralins whose availability as pure isomers attested to the stringent stereochemical requirements for selectivity at non-beta 1, non-beta 2 beta-adrenoceptors. Acceptance of the functionally based concept of a beta 3-adrenoceptor was boosted on structural grounds by molecular biology studies. Sequence analysis indicated the existence in humans and rodents of genes coding for a third subtype of beta-receptor that, when expressed in transfected heterologous cells, had a pharmacological profile distinct from the previously established subtypes. Finally, aryloxypropanolaminotetralins have been prepared as the first selective antagonists of beta 3-adrenoceptors, thus providing unambiguous conclusive evidence of the distinctive functional features of those abundant in the rat colon. The therapeutic potential in gastroenterology of the newer compounds targetable on the beta 3-adrenoceptor is suggested by their potent intestinal action in vivo in animal models without any of the cardiovascular or other unwanted effects of conventional beta-adrenoceptor agonists and antagonists, and by the clinically confirmed importance of beta-adrenergic control of motor function throughout the alimentary canal. However, open questions include the incidence of species-related differences in beta 3-adrenoceptors, and as yet there are no data on gastrointestinal functions in humans under the influence of drugs designed to act selectively at these receptors.

Site-specific effects of sympathectomy on the adrenergic control of lipolysis in hamster fat cells.

Regional variations in the response of adipose tissue to lipolytic stimuli have been suggested to be involved in the development of visceral adiposity-related morbidity and mortality. Moreover, studies in humans and in laboratory rodents such as hamsters have shown that the response of adipocytes to catecholamines depends on their anatomical origin. The aim of the present study was to investigate the relative involvement of the adrenal medulla and of the sympathetic nervous system on regional differences in the adrenergic control of lipolysis in isolated adipocytes from inguinal and epididymal adipose tissues. For this purpose, we carried out adrenal demedullation or chemical sympathectomy in hamsters. The results confirmed that epididymal adipocytes were significantly more responsive to to a beta-adrenergic stimulation than inguinal adipocytes (p < or = 0.05). This site specificity could originate at a step distal to receptors since tissues exhibited a similar number of binding sites for [125I]cyanopindolol. No significant regional differences were observed in the alpha2-adrenergic antilipolytic response, with the exception of the clonidine EC50. A 14-day sympathectomy significantly increased the beta-adrenergic lipolytic response only in inguinal adipocytes (p < or = 0.05), and increased the alpha2-adrenergic response only in epididymal adipocytes (p < or = 0.05). On the other hand, adrenal demedullation had no effect on both adrenergic pathways. These results suggest that the sympathetic tone of adipose tissues could be involved in the alpha2- and beta-adrenergic site-specific response in hamster fat cells. The 33% increase of the beta-response in inguinal fat cells and the 38% increase of the alpha2-response in epididymal fat cells also suggest that the sympathetic pathway favors the lipolytic activation of the epididymal adipose tissue.

Modulation of α1-adrenergic contractility in isolated vascular tissues by heptanol: A functional demonstration of the potential importance of intercellular communication to vascular response generation

After years of intensive investigation, the mechanism(s) underlying syncytial vascular smooth muscle responses both in vitro and in vivo is still poorly understood. Neither perivascular innervation nor regenerative electrical events appear sufficient to coordinate responses among vascular smooth muscle cells in many blood vessels. The implication of these observations is that another mechanism is required for organizing syncytial vascular responses. Although gap junctions are ubiquitously distributed among vascular wall cells throughout the vascular tree, their contribution to the modulation of vasomotor tone is still considered controversial. Resolution of the long standing debate awaits a clear demonstration that gap junctions modulate contraction or relaxation responses to vascular smooth muscle. Despite the absence of specific gap junctional uncoupling agents, it has still been possible to identify reasonable experimental conditions under which the contribution of gap junctions to contractile responses in isolated vascular tissues could be evaluated. Studies in isolated preparations known to contain gap junctions have indicated that alpha 1-adrenergic receptor-mediated contractile responses of diverse isolated vascular tissues, are significantly modulated by selective disruption of intercellular communication with the well studied lipophilic uncoupling agent heptanol. Interpretation of these pharmacological studies is explicitly dependent on the selectivity of the uncoupling actions of heptanol. Considerable experimental evidence suggests that, at the concentrations used, in the preparations thus far examined, heptanol does indeed have selective uncoupling actions. In fact, recent experiments provide empirical support for an operational definition of the selectivity of heptanol, and a functional role for gap junctions in modulating contractile responses in isolated vascular tissues. The operational definition states only that there exists a narrow, albeit identifiable, concentration range over which it is reasonable to assume that the effects of heptanol are primarily related to its uncoupling actions on gap junctions. The functional role for gap junctions is defined by their requisite contribution to tension development during contraction of isolated tissues. Experimentally, this can be visualized as a significant diminution in the contractile responses of isolated vascular tissues in the presence of selective uncoupling heptanol concentrations. Thus, a cogent interpretation of available data is that they provide compelling indirect evidence for a principle role of gap junctions in modulating the alpha 1-adrenergic contractility of isolated vascular tissues.

Partial restoration of impaired alpha 1-adrenergic responsiveness in parotid cells of aged rats by S-adenosylmethionine treatment.

The age related decrease in alpha 1-adrenergic stimulated inositol 1, 4, 5 trisphosphate (IP3) production in parotid cells of aged rats can be partially restored by treatment with S-adenosylmethionine (SAM). This effect is completely blocked by S-adenosyl homocysteine (SAH) and occurs in association with an increase in the conversion of phosphatidylethanolamine to phosphatidylcholine and a decrease in membrane viscosity. In contrast, SAM treatment actually inhibits stimulated IP3 production in cells of young rats. The membrane viscosity of these cells is lower than that of those from aged rats. Although conversion of phosphatidylethanolamine to phosphatidylcholine is enhanced, no further decrease in membrane viscosity is elicited in young cell preparations. These findings suggest that age changes in the membrane environment may result in impaired alpha 1-adrenergic signal transduction and that such alterations may be at least partially reversible by SAM treatment.

Vascular alpha-adrenergic responsiveness is reduced in cirrhosis.

Cirrhosis of the liver is associated with altered cardiovascular regulation. Patients with cirrhosis often have decreased total peripheral vascular resistance despite increased sympathetic activity. To determine whether this reduction in effective sympathetic activity may be caused by an alteration in vascular adrenergic responsiveness, we studied nine patients with biopsy-proven cirrhosis and 12 age-matched control subjects. To assess human vascular adrenergic responsiveness, we used dorsal hand vein linear variable differential transformer techniques. Sensitivity for phenylephrine-mediated vasoconstriction was significantly reduced in patients with cirrhosis (median effective dose [ED50] for phenylephrine: cirrhosis, 1514 ng/min; control subjects, 282 ng/min; p = 0.026). In contrast, the effect of isoproterenol did not differ (cirrhosis: 89% +/- 15% of maximal nitroglycerin effect; control subjects 79% +/- 6%; ED50 for isoproterenol: cirrhosis, 38 ng/min; control subjects, 20 ng/min). These studies indicate that vascular alpha-adrenergic responsiveness in patients with cirrhosis is decreased, whereas beta-adrenergic responsiveness remains intact. A selective decrease in vascular alpha-adrenergic responsiveness may contribute to the decreased peripheral vascular resistance in cirrhosis.

Effects of Exercise Training on -Adrenergic Mediated Pressor Responses and Baroreflex Function in Older Subjects

Endurance exercise training increases maximal O2 uptake (VO2max) in older subjects, and training also improves cardiac function in older men. Although the effects of training on beta-adrenergic responses have been investigated, little information is available regarding the effects of alpha-adrenergic responses and baroreflex function in older men and women. The purpose of the study was to determine whether endurance exercise training can affect alpha-adrenergic responses and baroreflex function in the elderly. We studied 13 men and women, 63 +/- 4 yrs old (mean +/- SE). VO2max was determined during treadmill exercise. Baroreflex function was determined from the change in heart rate (HR) relative to the change in systolic blood pressure (delta HR/delta SBP) during infusion of phenylephrine. VO2max was increased by 23% (1.9 +/- 0.16 vs 2.34 +/- 0.20 l/min; p < .01) in response to training. Maximal heart rate did not change, but HR during submaximal exercise at the same absolute exercise intensity was 17% lower after training. Resting heart rate was slower in the trained state. During alpha-adrenergic stimulation induced by graded doses of phenylephrine infusion, heart rate was lower after training because of training-induced bradycardia at rest. However, the elevation in systolic blood pressure (delta SBP) and mean blood pressure (delta MBP) from basal levels in response to a given dose of phenylephrine were significantly larger (delta SBP:18 +/- 3 vs 26 +/- 3 mmHg, p < .01; and delta MBP 10 +/- 2 vs 15 +/- 3 mmHg, p < .01) after than before training.(ABSTRACT TRUNCATED AT 250 WORDS)

Switching from α1- to β-subtypes in adrenergic response during primary culture of adult-rat hepatocytes as affected by the cell-to-cell interaction through plasma membranes

The alpha 1-adrenergic response was predominant over the beta-adrenergic one in adult rat hepatocytes, when the responses were measured as the agonist-induced generations of Ins(1,4,5)P3 and cyclic AMP, respectively. During primary culture of the adult rat hepatocytes, the beta-adrenergic response developed rapidly, whereas the alpha 1-response decreased gradually. Such receptor-subtype switching did not occur unless the cells were cultured under conditions favourable for cell growth, i.e. at low cell density (10(4) cells/cm2). The switching was prevented progressively as the cell culture density was increased up to 20-fold or the low-density culture was achieved by addition of increasing amounts of liver plasma membranes. The gradual decrease in alpha 1-response was accounted for by a concurrent decrease in the receptor site density, whereas rapid development of the beta-response definitely preceded the increase in beta-ligand binding sites during the culture. This rapid development of the beta-response reflected enhanced coupling of the receptor to G-protein during the early stage of culture, as evidenced by the progressively developed ability of GTP to lower the affinity of beta-agonist binding to membranes prepared from these short-time-cultured hepatocytes.

Ramipril prevents hypersensitivity to phenylephrine in aorta from streptozotocin-induced diabetic rats

This study investigated the protective effect of the angiotensin converting enzyme inhibitor, ramipril, on endothelium-dependent responses in arteries from control (CON) and streptozotocin-induced (STZ) diabetic rats. Three hypotheses were tested: 1) there is an endothelium-dependent component to the increased alpha-adrenergic responsiveness characteristic of diabetes; 2) endothelium-dependent, acetylcholine-induced relaxation is attenuated in aorta from diabetic rats; and 3) ramipril (3 mg/kg daily in the food, 12-15 weeks) will prevent functional vascular changes in diabetic rats. Vascular function was assessed in aortic rings using standard muscle bath procedures for measurement of isometric force. Sensitivity to phenylephrine was increased in aortic rings from diabetic compared to control values [pD2 values (-log ED50): CON = 6.22 +/- 0.12, STZ = 7.54 +/- 0.11), and removal of the endothelium (-Endo) increased phenylephrine sensitivity (CON-Endo = 7.40 +/- 0.11, STZ-Endo = 8.32 +/- 0.18). The magnitude of the shift in responsiveness following endothelium removal was greatest in control rats. Ramipril treatment (Ram) partially normalized phenylephrine responsiveness in intact (STZ + Ram = 6.55 +/- 0.11) and denuded (STZ-Endo + Ram = 7.75 +/- 0.10) vessels. Vasodilatation to acetylcholine and nitroglycerin was not altered in diabetic rats nor was it affected by ramipril treatment. Diabetes increases contractile sensitivity to phenylephrine but not to vasodilators and chronic ramipril treatment prevents this increase in contractile sensitivity. Ramipril treatment did not alter the hyperglycaemic condition induced by streptozotocin. The changes in phenylephrine sensitivity appear to involve an endothelial and a smooth muscle component.

Catecholamine stimulated lipolysis in differentiated human preadipocytes in a serum-free, defined medium.

Adipocyte precursors from the stromal vascular fraction of human adipose tissue were allowed to differentiate in serum-free defined medium, whereafter their catecholamine stimulated lipolytic response was compared to that of mature isolated human adipocytes. Seventy-five to ninety percent of the fibroblast-like cells accumulated lipid droplets and glycerol-3-phosphate dehydrogenase activities of 1,000-2,800 mU/mg protein were measured in cell homogenates of differentiated cells. Lipolysis could be stimulated by both isoproterenol and norepinephrine in both differentiated preadipocytes as well as mature adipocytes. The results obtained with beta-adrenergic agents suggested the presence of a higher affinity receptor in differentiated preadipocytes as compared to mature adipocytes. Mature adipocytes responded well to beta-adrenergic agents, but no antilipolytic alpha 2-adrenergic response was observed in the differentiated preadipocytes. The presence of Gi proteins in the differentiated preadipocytes was suggested by the antilipolytic effect of adenosine as well as the lipolytic activity generated by pertussis toxin. In conclusion, our medium supported the differentiation of a very high percentage of human preadipocytes which developed a sensitive beta-adrenergic lipolytic response but which lacked an alpha 2-adrenergic antilipolytic response.

Relationship between arterial blood pressure disturbances and alpha adrenoceptor density.

To investigate the influence of blood pressure disturbances on human platelet alpha 2-adrenoceptor density, we studied 7 normotensive Parkinsonians with orthostatic hypotension and 23 mild essential hypertensive patients. Plasma catecholamine levels were measured by HPLC and alpha 2-adrenoceptor number and affinity determined by [3H]-yohimbine binding. Alpha-adrenergic reactivity was investigated by blood pressure response to noradrenaline infusion in Parkinsonians and by adrenaline-induced platelet aggregation in hypertensive patients. In Parkinsonians with orthostatic hypotension, in comparison with Parkinsonians without orthostatic hypotension and normotensive control subjects age and sex matched, noradrenaline plasma levels were significantly lower (62 +/- 11, 195 +/- 14 and 219 +/- 13 pg. ml-1 respectively, p < 0.05), platelet alpha 2-adrenoceptor number was significantly higher (313 +/- 52, 168 +/- 9 and 174 +/- 4 fmol.mg-1 protein respectively, p < 0.05) and the noradrenaline dose required for a 25 mm Hg increase of systolic blood pressure significantly lower (0.19 +/- 0.03, 0.86 +/- 0.11 and 0.68 +/- 0.10 microgram.Kg-1 respectively, p < 0.05). In hypertensive patients, in comparison with normotensive control subjects age and sex matched, plasma noradrenaline levels remained unchanged (306 +/- 68 vs 246 +/- 28 pg.ml-1) whereas both platelet alpha 2-adrenoceptor number (137 +/- 15 vs 177 +/- 15 fmol.mg-1 protein, p < 0.05) and velocity of adrenaline-induced platelet aggregation were significantly decreased. These results indicate that platelet alpha 2-adrenoceptor density is related to blood pressure values. In Parkinsonians with orthostatic hypotension, the up-regulation of alpha 2-adrenoceptors was induced by the decrease of endogenous catecholamines. In contrast, in essential hypertension a down-regulation of alpha 2-adrenoceptors was observed in spite of no significant increase of catecholamine levels. These results suggest that only sustained abnormal plasma noradrenaline levels could allow the development of alpha 2-adrenoceptor regulatory mechanisms.

Effect of specific membrane perturbations on alpha 1-adrenergic and muscarinic-cholinergic signal transduction in rat parotid cell aggregates

Alpha 1-adrenergic and muscarinic-cholinergic stimulated IP 3 production and calcium mobilization are inhibited by treatment of parotid cell aggregates with methanol, hydrogen peroxide and saponin. Only methanol exerts an effect on binding to receptors. In most cases a close correspondence exists between inhibition of alpha 1-adrenergic and muscarini-cholinergic responses as well as inhibition of IP 3 production and calcium mobilization. G-protein dependent signal transduction, therefore appears to be quite sensitive to plasma membrane perturbation and membrane active agents may provide useful tools for elucidation of transduction mechanisms and their regulation.

Effects of wortmannin on alpha-1/alpha-2 adrenergic receptor-mediated contractile responses in rabbit vascular tissues.

The inhibitory effect of wortmannin (WO), a fungus-derived protein kinase inhibitor, was assessed on contractile responses elicited by phenylephrine-induced alpha 1-(alpha 1 R) and UK 14304-induced alpha 2-adrenergic receptor (alpha 2R) stimulation in the rabbit aorta and saphenous vein, respectively. In agonist dose-response studies, WO caused a noncompetitive inhibition of both alpha 1R and alpha 2R responses, but was more potent against alpha 2R. Maximally effective single-dose responses at both receptors were less sensitive to WO. The initial alpha 1R contractile response, associated with intracellular Ca2+ release and myosin light chain kinase activation, was relatively insensitive to WO, while the Ca2+ influx-dependent tonic contraction was more sensitive. Contractions induced by high K+ buffer were relatively insensitive to WO in both the aorta and saphenous vein. These results indicate that WO inhibits receptor-initiated Ca2+ influx-dependent contractile responses such as those caused by alpha 2R stimulation and the sustained phase of alpha 1R stimulation more readily than Ca2+ release-dependent responses.

Alteration of response to neuropeptide Y in the nucleus tractus solitarius of spontaneously hypertensive rats.

In normotensive rats, microinjections of neuropeptide Y (2.5 to 25 pmol) into the unilateral nucleus tractus solitarius elicited dose-dependent vasodepressor and bradycardiac responses accompanied by an inhibition of sympathetic nerve firing. After microinjections of the alpha 2-adrenergic receptor antagonist yohimbine (100 ng) into the nucleus tractus solitarius, the depressor and bradycardic responses to the injection of neuropeptide Y (25 pmol) into the nucleus tractus solitarius were significantly attenuated. In contrast, pretreatment with the alpha 1-adrenergic receptor antagonist doxazosin (200 ng) injected into the nucleus tractus solitarius did not alter these responses. In spontaneously hypertensive rats, microinjections of neuropeptide Y (25 pmol) into the nucleus tractus solitarius also elicited depressor and bradycardic responses that were significantly less than those of normotensive Wistar-Kyoto rats. However, pretreatment with yohimbine (100 ng) in the nucleus tractus solitarius did not diminish these depressor responses in spontaneously hypertensive rats. Depressor responses to neuropeptide Y, which was administered after yohimbine pretreatment, were also less in Wistar-Kyoto rats than in spontaneously hypertensive rats. The results suggest that the depressor and bradycardic responses elicited by neuropeptide Y were accompanied by the inhibition of sympathetic nerve activity. These responses may be mediated in part by alpha 2-adrenergic receptor in the nucleus tractus solitarius. The impairment of alpha 2-adrenergic receptor-mediated responses to neuropeptide Y in spontaneously hypertensive rats may contribute to the development of hypertension.

Responsiveness to alpha- and beta-adrenergic receptor agonists. Effects of race in borderline hypertensive compared to normotensive men.

The responsiveness of alpha- and beta-adrenergic receptors was assessed in 13 black and 13 white borderline hypertensive and normotensive men, matched for age and body mass. White borderline hypertensives showed significantly decreased responsiveness of cardiac beta-adrenergic receptors and vascular beta 2-adrenergic receptors to intravenous isoproterenol. In contrast, black borderline hypertensives showed no evidence of decreased beta-adrenergic receptor responsiveness. Vascular alpha 1-adrenergic receptor responsiveness, assessed by pressor response to phenylephrine, was unrelated to blood pressure, but was significantly greater in black than in white men. These preliminary observations suggest that there may be racial differences in adrenergic receptor mechanisms involved in the pathogenesis of hypertension.

Alpha 2-adrenergic inhibition of Cl- transport by opercular epithelium is mediated by intracellular Ca2+.

We isolated the opercular epithelium of sea-water killifish (Fundulus heteroclitus) to study the mediation of catecholamine inhibition of Cl- secretion. The receptors are alpha 2-adrenergic, as they have a high affinity for the alpha 2-adrenergic agonist clonidine over phenylephrine and clonidine action is blocked by yohimbine. Pertussis toxin and indomethacin did not block the clonidine effect; hence inhibitory guanine nucleotide-binding proteins (Gi proteins) and prostaglandins (respectively) are not involved. Intracellular pH (pHi) of single chloride cells was measured microspectrofluorometrically and resting pHi was 7.22 +/- 0.03. However, pHi was unaffected by clonidine; hence pHi and Na+/H+ exchange are not involved. The lipoxygenase inhibitors nordihydroguaiaretic acid and baicalein and the lipoxygenase products (12S)- and (12R)-12-hydroxyeicosatetraenoic acid stimulated Cl- secretion. Protein kinase C is an unlikely site of action because the diacylglycerol kinase inhibitor R59022 had no effect alone and did not block the clonidine effect. Ionomycin (1 microM) in normal but not low-Ca2+ solutions mimicked the action of clonidine and both inhibitions were reversible by isoproterenol. Thapsigargin, a releaser of intracellular Ca2+, inhibited Cl- secretion and this effect was reduced in low-Ca2+ solutions. Low-Ca2+ solutions also blunted but did not block entirely the clonidine response, indicating that the primary Ca2+ release was from intracellular stores. Whereas alpha 1-adrenergic receptors commonly act via the Ca2+/inositol trisphosphate pathway, to our knowledge this is the first report of a Ca(2+)-mediated alpha 2-adrenergic response in a nonmammalian vertebrate.

Inhibition of alpha-adrenergic responses in the rat liver by lipophilic K+ channel blockers or depolarizing Cl- gradients. Evidence for a potential-sensitive step in the signal transduction path.

To study the role of K+ channels and membrane potential in alpha-adrenergic responses of the rat liver, lipophilic K+ channel blockers quinidine and 4-aminopyridine were used or external Cl- was replaced with gluconate, an impermeant ion. Glucose release, O2 uptake, portal pressure, and K+ flux were measured in the isolated perfused liver. The alpha-agonist phenylephrine caused biphasic changes in each parameter, a fast transient followed by sustained elevated responses. Infusion of 5 mM 4-aminopyridine, 0.1 mM quinidine, or gluconate prior to phenylephrine inhibited each parameter, with the greatest inhibition occurring during the second phase. A similar pattern was seen with 2 mM EGTA. This contrasts with the full inhibition of all responses following exposure to the alpha-antagonist phentolamine. Infusion of each inhibitor at the peak of the sustained phase inhibited all responses. Phenylephrine-stimulated release of K+ was augmented in the presence of EGTA and was inhibited by 4-aminopyridine or quinidine. In contrast, beta-adrenergic stimulation of glucose release and K+ flux were not affected by the K+ channel blockers. Phenylephrine-stimulated glucose release from hepatocyte suspensions decreased by about 50% in the presence of 4-aminopyridine, EGTA, or gluconate. The results are discussed in terms of a potential role for K+ channels in alpha-adrenergic signal transduction in the liver.

Homologous upregulation of human arterial alpha-adrenergic responses by guanadrel.

The purpose of this study was to test the hypothesis that there is homologous upregulation of arterial alpha-adrenergic responsiveness during suppression of sympathetic nervous system (SNS) activity in humans. 10 subjects (19-28 yr) were studied during placebo and when SNS activity was suppressed by guanadrel. Changes in forearm blood flow (FABF) mediated by the intraarterial infusion of norepinephrine (NE), angiotensin II (AII), and phentolamine were measured by plethysmography. During guanadrel compared with placebo, plasma NE levels (1.28 +/- 0.09-0.85 +/- 0.06 nM; P = 0.0001) and the extra vascular NE release rate derived from [3H]NE kinetics were lower (7.1 +/- 0.7-4.0 +/- 0.2 nmol/min per m2; P = 0.0004), suggesting suppression of SNS activity. During guanadrel, there was increased sensitivity in the FABF response to NE (analysis of variance P = 0.03). In contrast, there was no difference in the FABF response to AII (analysis of variance P = 0.81), suggesting that the upregulation observed to NE was homologous. The increase in FABF during phentolamine was similar during guanadrel compared with placebo (guanadrel: 141 +/- 37 vs. placebo; 187 +/- 27% increase; P = 0.33), suggesting that there was at least partial compensation to maintain constant endogenous arterial alpha-adrenergic tone. We conclude that there is homologous upregulation of arterial alpha-adrenergic responsiveness in humans when SNS activity is suppressed by guanadrel.

The relationship between the ambulatory variability and the laboratory reactivity of blood pressure and heart rate.

We examined the relationship between the ambulatory variability and the laboratory reactivity of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) in 21 male college students. The mean increase during the waking period from that during sleep was defined as variability 1, and the standard deviation of the ambulatory measurements during waking was defined as variability 2. The reactivity to laboratory tests was measured by the pretask-to-task increase in variables. The high SBP variability 1 group showed a significantly higher reactivity of SBP and noradrenaline in the bicycle exercise test (70w). This suggests the possibility that SBP variability 1, can be predicted by increased reactivity to a mild limb exercise test. The high HR variability 1 group, and the high SBP variability 2 group showed significantly lower reactivity of stroke volume (SV) and cardiac output (CO) in the cold face test. Thus, parasympathetic responses such as trigeminal-brainstem-vagal pathway function or baroreflex sensitivity seemed to be reduced in these groups. The high DBP variability 2 group showed significantly lower DBP reactivity in the cold face test, and low noradrenaline reactivity in the mental arithmetic test, which indicated a reduced alpha-adrenergic response in this group. No other significant differences in reactivity to the laboratory mental stress tests were found between the variability 1 and variability 2 groups.

Vasodilators inhibit acute alpha 1-adrenergic receptor-induced trophic responses in the vasculature.

Cardiovascular hypertrophy plays an important role in the development and maintenance of hypertension. Hyperactivity of the sympathetic nervous system may be one of the initiating factors responsible for the stimulation of growth processes involved in these structural alterations. We have used a well-established early biochemical marker of cellular growth processes, induction of ornithine decarboxylase (ODC), to determine whether alpha 1-adrenergic receptor-induced vascular trophic responses are dependent on arterial pressure elevation. Hydralazine or felodipine were coadministered to control the alpha 1-adrenergic receptor agonist-induced rise in mean arterial pressure (MAP). Methoxamine (2, 5, or 10 mg/kg s.c.) increased the average MAP (up to 20 mm Hg) and vascular ODC activity (up to ninefold) above control rats over 4 hours. Concomitant administration of hydralazine (0.5, 1.25, or 5 mg/kg s.c.) or felodipine (100 or 250 micrograms/kg s.c.) with methoxamine (10 mg/kg) attenuated the alpha 1-adrenergic receptor-induced activation of ODC in the aorta and mesenteric resistance vasculature, as well as the MAP increases. Vasodilators alone did not lower basal vascular ODC activity. The major findings include: 1) alpha 1-adrenergic receptor activation dose-dependently induces vascular ODC activity concomitantly with MAP elevation, 2) vasodilators inhibited both the alpha 1-adrenergic receptor-induced MAP increases and the activation of mesenteric vascular and aortic ODC, and 3) the stimulus-response correlation between MAP elevation and mesenteric (r = 0.78) and aortic (r = 0.92) ODC activation was characterized by a logistic function.(ABSTRACT TRUNCATED AT 250 WORDS)