Attempts to uncover subtypes of α-adrenoceptors and associated mechanisms by using sequential administration of blocking drugs

1985 ◽  
Vol 68 (s10) ◽  
pp. 25s-30s ◽  
Author(s):  
T. L. Grant ◽  
N. A. Flavahan ◽  
J. Greig ◽  
J. C. McGrath ◽  
C. E. McKean ◽  
...  

1. By the sequential administration of α1- and α2-blockers it can be shown, in the pithed rabbit, that the dose/pressor response curve to noradrenaline consists of two separate curves, one for each receptor. α2-mediated responses predominate at low doses and α1-mediated responses predominate at high doses. Pressor responses to sympathetic nerve stimulation have, similarly, an α2 component at low frequencies and a dominant α1-mediated response at high frequencies: a residual response is resistant to combined α1- plus α2-blockade. 2. This α-blocker-resistant pressor nerve response was further analysed in the pithed rat and was found to be partly susceptible to α,β-methylene ATP, which densitizes purinergic responses. However, reserpine pretreatment produced a greater reduction of nerve-mediated pressor responses than did α-blockade, suggesting that part of the ‘α-blocker resistant’ response might be adrenergic. 3. It is concluded that sympathetic vasopressor nerve transmission is mediated for the greater part by α1- and α2-adrenoceptors but that there is evidence for contributions from non-α-adrenergic and ‘purinergic’ elements. An even greater proportion of the responses to circulating catecholamines is attributable to the α-receptors with a relatively small but significant ‘resistant’ component.

1990 ◽  
Vol 258 (5) ◽  
pp. R1147-R1156 ◽  
Author(s):  
K. C. Tomlinson ◽  
S. M. Gardiner ◽  
T. Bennett

Responses to intracerebroventricular (icv) angiotensin II (ANG II) were measured in Long-Evans rats treated with the diabetogenic agent, streptozotocin (STZ), or saline 28 days earlier. STZ-treated Long-Evans rats showed normal pressor responses to ANG II in the absence of drinking water, but bradycardic responses were impaired although there was no reduction in baroreflex sensitivity. When allowed to drink, saline-treated, but not STZ-treated, rats showed an enhanced pressor response to icv ANG II and a tachycardia. Peripheral V1-receptor antagonism attenuated the pressor response to icv ANG II, leaving a residual response that was greater in saline-treated than in STZ-treated rats. STZ-treated rats had attenuated pressor and heart rate responses to icv angiotensin I (ANG I). Although some cardiovascular responses to icv ANG I and ANG II were reduced in STZ-treated rats, these animals showed enhanced sensitivity to the dipsogenic effects of the peptides. Vasopressin-deficient Brattleboro rats showed little pressor response to icv ANG II unless drinking was allowed, in which case the pressor response was less in STZ-treated than in saline-treated Brattleboro rats, although there was no difference in drinking response.


1997 ◽  
Vol 272 (5) ◽  
pp. H2146-H2153 ◽  
Author(s):  
J. L. Hall ◽  
J. M. Ye ◽  
M. G. Clark ◽  
E. Q. Colquhoun

The effects of lumbar sympathetic nerve stimulation on oxygen uptake (VO2) in curarized muscle of the perfused rat hindlimb were investigated. Stimulation of sympathetic nerves elicited vasoconstriction at all frequencies. Importantly, this was associated with changes in VO2 that were generally stimulatory at low frequencies (0.5-2 Hz) and inhibitory at high frequencies (5-10 Hz). Both the pressor response and the changes in VO2 were almost completely blocked by the alpha 1/alpha 2-blocker phentolamine (1.0 microM) but were not affected by the beta 1/beta 2-blocker DL-propranolol (2.0 microM). The alpha 2-blocker yohimbine (0.1 microM) did not significantly affect either the pressor or VO2 response. The alpha 1-antagonist prazosin (0.1 microM) abolished the vasoconstriction with low-frequency stimulation and inhibited > 90% of the vasoconstriction with high-frequency stimulation. Intra-arterial infusion of phenylephrine (alpha 1-agonist), but not of UK-14304 (alpha 2-agonist), also elicited a similar biphasic response in VO2 during vasoconstriction. The changes in VO2 at both low- and high-frequency stimulation were fully reversed by prazosin. The vasodilator sodium nitroprusside also showed similar effects to prazosin in blocking both VO2 and vasoconstriction. Thus sympathetic control of VO2 in the perfused rat hindlimb appears to be initiated by activation of predominantly vascular alpha 1-adrenoceptors.


1988 ◽  
Vol 254 (1) ◽  
pp. R75-R77
Author(s):  
D. Gazis ◽  
G. Gonzalez ◽  
M. Mendlowitz

The effects of the calcium channel blocker verapamil on simultaneously recorded uterine and pressor responses to the equipotent (in eliciting these responses) oxytocin-vasopressin analogue, oxypressin, were studied in urethan-anesthetized and pentolinium- and indomethacin-treated rats during injections and infusions of this analogue. Doses of verapamil that almost completely blocked the pressor response to infused oxypressin had no effect on a pressor response to injected oxypressin of equal magnitude. Larger doses of verapamil blocked the pressor response to injected oxypressin somewhat. Uterine responses were only marginally affected by these doses of verapamil, and there was no significant difference between infusion and injection or between estrus and diestrus.


2015 ◽  
Vol 804 ◽  
pp. 25-29 ◽  
Author(s):  
Wanlop Harnnarongchai ◽  
Kantima Chaochanchaikul

The sound absorbing efficiency of natural rubber (NR) foam is affected by the cell morphology of foam. Potassium oleate (K-oleate) and sodium bicarbonate (NaHCO3) were used as blowing agents to create open-cell foam. Amounts of the blowing agent were varied from 0.5 to 8.0 part per hundred of rubber (phr) to evaluate cell size and number of foam cell as well as sound adsorption coefficient of NR foam. The NR foam specimens were prepared using mould and air-circulating oven for vulcanizing and foaming processes. The results indicated that K-oleate at 2.0 phr and NaHCO3 at 0.5 phr led to form NR foam with the smallest cell size and the largest number of foam cell. At low frequencies, the optimum sound adsorption coefficient of NR foam was caused by filling K-oleate 2 phr. However, that of NR foam at high frequencies was provided by 0.5 phr-NaHCO3 addition.


1993 ◽  
Vol 107 (3) ◽  
pp. 179-182 ◽  
Author(s):  
J. R. Cullen ◽  
M. J. Cinnamond

The relationship between diabetes and senbsorineural hearing loss has been disputed. This study compares 44 insulin-dependent diabetics with 38 age and sex matched controls. All had pure tone and speech audiometry performed, with any diabetics showing sensorineural deafness undergoing stapedial reflecx decat tests. In 14 diabetics stapedial reflex tests showed no tone decay in any patient, but seven showed evidence of recruitment. Analysis of vaiance showed the diabetics to be significantly deafer than the control population.The hearing loss affected high frequencies in both sexes, but also low frequencies in the male. Speech discrimination scores showed no differences. Further analysis by sex showed the males to account for most of the differences. Analysys of the audiograms showered mostly a high tone loss. Finally duration of disbetes, insulin dosage and family history of diabtes were not found to have a significant effect on threshold.


Author(s):  
Jerome E. Manning

Abstract Statistical energy analysis provides a technique to predict acoustic and vibration levels in complex dynamic systems. The technique is most useful for broad-band excitation at high frequencies where many modes contribute to the response in any given frequency band. At mid and low frequencies, the number of modes contributing to the response may be quite small. In this case SEA predictions show large variability from measured data and may not be useful for vibroacoustic design. This paper focuses on the use of measured data to improve the accuracy of the predictions. Past work to measure the SEA coupling and damping loss factors has not been successful for a broad range of systems that do not have light coupling. This paper introduces a new hybrid SEA technique that combines measured mobility functions with analytical SEA predictions. The accuracy of the hybrid technique is shown to be greatly improved at mid and low frequencies.


Author(s):  
Gundula B. Runge ◽  
Al Ferri ◽  
Bonnie Ferri

This paper considers an anytime strategy to implement controllers that react to changing computational resources. The anytime controllers developed in this paper are suitable for cases when the time scale of switching is in the order of the task execution time, that is, on the time scale found commonly with sporadically missed deadlines. This paper extends the prior work by developing frequency-weighted anytime controllers. The selection of the weighting function is driven by the expectation of the situations that would require anytime operation. For example, if the anytime operation is due to occasional and isolated missed deadlines, then the weighting on high frequencies should be larger than that for low frequencies. Low frequency components will have a smaller change over one sample time, so failing to update these components for one sample period will have less effect than with the high frequency components. An example will be included that applies the anytime control strategy to a model of a DC motor with deadzone and saturation nonlinearities.


2000 ◽  
Vol 39 (10) ◽  
pp. 1645-1656 ◽  
Author(s):  
Gail M. Skofronick-Jackson ◽  
James R. Wang

Abstract Profiles of the microphysical properties of clouds and rain cells are essential in many areas of atmospheric research and operational meteorology. To enhance the understanding of the nonlinear and underconstrained relationships between cloud and hydrometeor microphysical profiles and passive microwave brightness temperatures, estimations of cloud profiles for an anvil region, a convective region, and an updraft region of an oceanic squall were performed. The estimations relied on comparisons between radiative transfer calculations of incrementally estimated microphysical profiles and concurrent dual-altitude wideband brightness temperatures from the 22 February 1993 flight during the Tropical Ocean and Global Atmosphere Coupled Ocean–Atmosphere Response Experiment. The wideband observations (10–220 GHz) are necessary for estimating cloud profiles reaching up to 20 km. The low frequencies enhance the rain and cloud water profiles, and the high frequencies are required to detail the higher-altitude ice microphysics. A microphysical profile was estimated for each of the three regions of the storm. Each of the three estimated profiles produced calculated brightness temperatures within ∼10 K of the observations. A majority of the total iterative adjustments were to the estimated profile’s frozen hydrometeor characteristics and were necessary to match the high-frequency calculations with the observations. This requirement indicates a need to validate cloud-resolving models using high frequencies. Some difficulties matching the 37-GHz observation channels on the DC-8 and ER-2 aircraft with the calculations simulated at the two aircraft heights (∼11 km and 20 km, respectively) were noted, and potential causes were presented.


1989 ◽  
Vol 257 (3) ◽  
pp. H918-H926 ◽  
Author(s):  
M. M. Knuepfer ◽  
S. P. Han ◽  
A. J. Trapani ◽  
K. F. Fok ◽  
T. C. Westfall

Endothelin is a peptide with potent, long-lasting pressor effects characterized by increases in mesenteric and hindquarters vascular resistance and bradycardia following an initial, transient depressor response. This study examined the mechanisms of action of endothelin on regional hemodynamics in conscious, freely moving rats and on baroreflex sensitivity both in conscious and chloralose-anesthetized rats. The pressor response to endothelin (0.67 nmol/kg) was attenuated by nifedipine (25 micrograms/kg) and augmented by chloralose anesthesia. The bradycardia was attenuated by pentolinium (10 mg/kg), atropine methyl sulfate (0.5 mg/kg), or chloralose anesthesia. Hindquarter vaso-constriction was attenuated by nifedipine, pentolinium, and atropine, whereas mesenteric vasoconstriction was less sensitive to blockade. The vasopressin V1 antagonist, [d(CH2)5Tyr(Me)]-AVP (20 micrograms/kg), indomethacin (5 mg/kg), or verapamil (150 micrograms/kg) did not affect any of these cardiovascular responses. Renal sympathetic nerve activity was reduced similarly in chloralose-anesthetized rats to pressor responses elicited by either phenylephrine or endothelin, and the slope of the baro-reflex function curve after endothelin was similar to that of phenylephrine. These results suggest that endothelin is a potent vasoconstrictor in which its action on visceral and skeletal muscle vasculature is mediated by somewhat different mechanisms. Endothelin does not alter baroreceptor reflex control of sympathetic nerve activity or heart rate.


1985 ◽  
Vol 249 (1) ◽  
pp. E49-E55 ◽  
Author(s):  
R. P. Naden ◽  
S. Coultrup ◽  
B. S. Arant ◽  
C. R. Rosenfeld

Reduced vascular responsiveness to infused angiotensin II (ANG II) has been observed during pregnancy. It has been proposed that infusions produce lower circulating concentrations of ANG II in pregnancy, due to an increase in the metabolic clearance rate of ANG II (MCRangii). We have evaluated the MCRangii and the arterial plasma concentrations of ANG II during constant infusions of 1.15 micrograms ANG II/min into chronically instrumented pregnant (n = 6) and nonpregnant (n = 9) sheep. Although the pressor responses were significantly less in the pregnant than in the nonpregnant sheep (17.5 +/- 0.5 vs. 34.9 +/- 3.2 mmHg, P less than 0.001), the values for MCRangii were not different: 56.2 +/- 6.3 ml X min-1 X kg-1 in nonpregnant and 55.9 +/- 4.3 ml X min-1 X kg-1 in pregnant sheep. The steady-state plasma ANG II concentrations during the infusions were slightly less in pregnant than in nonpregnant sheep (388 +/- 36 vs. 454 +/- 36 pg/ml); however, this difference would be responsible for only a 2-mmHg reduction in the pressor response. We conclude that the reduced pressor response to infused ANG II in pregnancy is not due to an increase in MCRangii nor to lower plasma ANG II concentrations.


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