The effects of the Ca entry blockers nifedipine and verapamil on the contractions induced by phenylephrine (PHE) in rat isolated aorta and mesenteric vascular bed (MVB) were evaluated. The main goal was to elucidate whether differences among blood vessels in their receptor reserves are involved in the different degrees to which Ca antagonists inhibit alpha adrenergic vasoconstriction. In the two tissues the responses to the full agonist PHE were antagonized by prazosin with an at least 1000-fold greater potency than by yohimbine. The -log KB values for both antagonists in the aorta (11.07 and 7.40, respectively) were significantly higher than those in the MVB (9.77 and 6.43, respectively), thus suggesting receptor heterogeneity between the two tissues. Both nifedipine and verapamil were more effective in reducing the responses in the MVB (maximal inhibition, 54.3 +/- 1.9 and 55.0 +/- 3.5%) than in the aorta (25.2 +/- 5.8 and 30.4 +/- 0.7%). Studies with phenoxybenzamine (PB) indicated that in the latter case the responses were associated with an effective receptor reserve of about 40%, whereas in the MVB no spare receptors for the full agonist were available. Pretreatment of the MVB with PB showed no effect on the inhibitory action of verapamil. Conversely, removal of the spare receptors in the aorta (10(-10) M PB) rendered the responses more susceptible to inhibition by verapamil. Pretreatment of the aortic strips with 10(-9) M PB, however, failed to enhance further the effectiveness of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
minipress 2 mg
Aqueous extract of the stem of Gongronema latifolium was screened for effects on the gastrointestinal tract of rats and mice. On the isolated rat intestine, the extract (5-80 μg) evoked reproducible and concentration-related relaxation which were attenuated by yohimbine and phenoxybenzamine. Intraperitoneal (i.p.) administration of the extract in mice significantly reduced small intestinal transit dose-dependently. This effect was also attenuated by yohimbine and phenoxybenzamine, but not prazosin and propranolol. Phytochemical analysis revealed the presence of some bioactive constituents, while the i.p. LD(50) value of the extract in mice was established as 1678.63 ± 78 mg/kg. The results suggest the involvement of the alpha(2)-adrenoceptors in the effect of the extract on the intestinal function.
minipress xl dose
Aromatase in the diencephalic neurons, the level of which increases transiently during the prenatal to neonatal period, has been suggested to be involved in control of sexual behavior and differentiation of the CNS. Effects of neurotransmitters on levels of aromatase mRNA in cultured neurons were investigated to determine factors regulating the developmental increase that occurs in level of fetal brain aromatase. The expression of aromatase in diencephalic neurons of fetal mice at embryonic day 13, cultured in vitro, was significantly affected by alpha 1-adrenergic receptor ligands. Aromatase mRNA levels were higher in neurons treated with the alpha 1-agonist phenylephrine than in control neurons, whereas prazosin, an alpha 1-antagonist, suppressed this increase, and ligands for alpha 2- or beta-adrenergic receptors did not exert any influence. The profile of alpha 1-adrenergic receptor subtypes during actual development in vivo suggested that the alpha 1B subtype is in fact responsible for the signal transduction. Substance P, cholecystokinin, neurotensin, and brain natriuretic peptide also increased the level of expression along with phorbol 12-myristate 13-acetate and dibutyrylcyclic GMP, whereas forskolin and dibutyryl-cyclic AMP caused a decrease. These data indicate that stimulation via alpha 1 (possibly alpha 1B)-adrenergic receptors, as well as receptors of specific neuropeptides, controls the expression of aromatase in embryonic day 13 diencephalic neurons through activation of protein kinase C or G. beta-Adrenergic receptors would not appear to participate in the regulation, judging from their developmental profile, although cyclic AMP might be a suppressive second messenger.
Taken together, these results suggested that α1B -adrenoceptor signalling is required for bone formation and regulated cellular proliferation through a mechanism relevant to the up-regulation of Cebpd in osteoblasts and, thus, provide new evidence for the physiological importance of α1B -adrenoceptor signalling in bone homeostasis.
1. Transport-P is an antidepressant-sensitive, proton-dependent, V-ATPase-linked uptake process for amines in peptidergic neurones of the hypothalamus. It is unusual in its anatomical location in postsynaptic neurones and in that it is activated by its substrate (prazosin). This study examined the structural properties of phenylethylamine derivatives which are substrates for transport-P, as judged by competitive inhibition of the uptake of prazosin 10(-6) M in immortalized hypothalamic peptidergic neurones. 2. A basic amine was essential for activity; absence of the amine or neutralization with a carboxyl group abolished activity. Primary, secondary and tertiary amines were active but quaternary and guanyl amines were inactive. 3. A phenyl group was essential for activity at transport-P. Potency at transport-P was reduced by phenolic hydroxyl groups and enhanced by phenolic halogens. Thus, for maximal potency, the phenyl group should be hydrophobic. Phenolic methoxyl groups had no effect on potency at transport-P. 4. A side chain was necessary for activity at transport-P. Potency at transport-P was reduced by beta-hydroxyl and enhanced by alpha-methyl groups. 5. These findings further distinguish transport-P from other amine uptake processes in the brain.
Stroke incidence and mortality rates are higher in the southeastern region of the United States, which is called the "Stroke Belt." We compared the response to antihypertensive medication use in patients from different US regions.
minipress ptsd dosage
1. The actions of BaCl2 and 4-aminopyridine, blockers of K+ channels, on the mechanical activity of the epididymal half of the rat vas deferens were investigated. 2. Both BaCl2 and 4-aminopyridine dose-dependently evoked phasic contractions. High extracellular potassium (35-40 mM) caused a tonic contraction but abolished the BaCl2- and 4-aminopyridine-induced phasic activity and reduced the BaCl2-induced sustained component of contraction, but increased the 4-aminopyridine-induced tonic contraction. 3. Omission of calcium from the extracellular medium totally abolished the 4-aminopyridine-induced response but only reduced the mean amplitude of phasic contractions induced by BaCl. 4. Procaine (10 mM), an inhibitor of internal calcium release, completely abolished the phasic activity and reduced the sustained contraction induced by BaCl2. The remaining tone was abolished by nifedipine (1 microM). 5. Tetraethylammonium (1 mM) suppressed the amplitude of the BaCl2-induced phasic contractions, and induced a biphasic increase in tonic tension. 6. The BaCl2-induced responses were resistant to prazosin (1 microM), yohimbine (3 microM), propranolol (3 microM) or atropine (3 microM); in contrast, the 4-aminopyridine-induced activity was effectively inhibited by prazosin (1 microM) attenuated by yohimbine (1 microM) and atropine (1 microM) but not by propranolol (3 microM). The 4-aminopyridine-induced response was abolished by pretreatment of the vas deferens with 6-hydroxydopamine (0.5 mM). 7. The results indicate that the BaCl2-evoked activity in the vas deferens was mainly due to blockade of Ba(2+)-sensitive K+ channels on the smooth muscle plasma membrane. Subsequent calcium entry through the depolarized plasma membrane was needed to trigger generation of phasic contractions. 4-Aminopyridine-induced action, however, was largely mediated by neurotransmitters released from the depolarized nerve terminals as a result of blockade of K+ channels.
Male Sprague-Dawley rats, which are prone to develop diet-induced obesity (DIO) on a high energy (HE) diet can be separated from rats which are diet-resistant (DR) by several prospective tests. Using such tests, chow-fed DRl-prone rats have higher binding of 3H paraminoclonidine (PAC) to brain alpha2-adrenoceptors than do DIO-prone rats. These differences disappear after 3 months on a HE diet. To study the predictive value of these tests and possible associated changes in presynaptic membrane composition, brain alpha3(1-) (1nM 3H prazosin) and (alpha2-adrenoceptor (1nM) 3-H PAC) binding and synaptosomal fatty acid composition were assessed in 3-month-old male rats separated by weight gain into DR and DIO groups after 1 month on a HE diet. DIO had comparable total caloric intake but gained 30% and 43% more weight and were hyperinsulinemic compared to DR and chow-fed rats, respectively. After 1 month on a HE diet, DR rats still had 15%-53% higher 3H PAC binding than DIO and/or chow-fed rats in 14 of 16 brain areas assessed. A phenotype effect was present primarily in the amygdala where DR rats had higher 3H PAC binding than DIO rats. A diet effect was seen in some hypothalamic nuclei where both DR and DIO rats had higher 3H PAC binding than chow-fed rats. Conversely, DIO rats had 14%-21% higher 3H prazosin binding than DR rats in 3 brain areas. Changes in brain synaptosomal membranes' fatty acids reflected both phenotype and diet effects. Thus, while diet composition affects presynaptic membrane composition and alpha2-adrenoceptor binding in both DR and DIO rats, the predominance of plasticity of these parameters is limited to the brains of DR rats. This suggests that such plasticity may be an important determinant of the ability to resist the development of diet-induced obesity on a HE diet.
tab minipress dose
1. Peristaltic contractions were induced in segments of rat ileum by raising the intramural pressure. A mean pressure of 4.3 +/- 0.2 cmH2O (n = 112) was required to initiate rhythmic contractions of the longitudinal muscle (preparatory phase) and associated volume expulsions caused by circular muscle contraction. The frequency of peristalsis remained constant over two 15 min periods of stimulation. 2. The alpha 2-adreoceptor agonists, clonidine, UK 14,304, B-HT 920, B-HT 933 and the selective alpha 2A-agonists, oxymetazoline and guanfacine, caused concentration-dependent inhibition of peristaltic contractions. The potency order and IC50 values (nM) were: clonidine (2.81) > or = oxymetazoline (4.23) > or = UK 14,304 (4.48) > or = guanfacine (5.51) > B-HT 920 (78.72) > B-HT 933 (442.48). 3. High concentrations of clonidine, amounting to more than 10 and 100 times the IC50 value in the peristaltic reflex (30 and 300 nM respectively), failed to inhibit the cholinergic contractile response to transmural electrical stimulation over the range of 2.5 to 40 Hz. 4. alpha 2-Adrenoceptor antagonists were used to determine the subtype of presynaptic alpha 2-adrenoceptor in rat ileum. All the antagonists tested caused parallel shifts to the right of the concentration-response regression line to clonidine and none, except ARC 239, influenced the rate of peristalsis. However, ARC 239 significantly decreased the frequency of control period peristaltic contractions. The order of affinity of the antagonists against clonidine (pKB values in parentheses) was RX 821002 (8.99) > phentolamine (8.07) > BRL 44408 (7.43) > or = rauwolscine (7.41) > or = yohimbine (7.28) > prazosin (5.86) > or = ARC 239 (5.74). 5. These results, when compared with binding and functional data from various other tissues and cell lines, are consistent with the presence of presynaptic alpha 2D-adrenoceptors in rat ileum. Further evidence is provided that this subtype of alpha 2-adrenoceptor is probably located proximal to the final cholinergic neurones in the reflex arc.