Interaction of the antihypertensive drug felodipine with calmodulin.
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Animals↗
Biomedical subjects
B Ljung
Publications and source records attributed to B Ljung.
Angiotensin I converting enzyme activity in portal vein studied in normotensive rats and in models of primary and secondary hypertension.
The effects of angiotensin I (AT I), angiotensin II (AT II) and the activity of AT I converting enzyme (ACE) were investigated in isolated portal veins of normotensive rats (WKR and NCR) and of rats with primary (SHR) and secondary (one clip 2 kidney renal; RHR) hypertension. Based on ED50 values, the tissue sensitivity to AT II was slightly less in the portal veins of RHR than SHR, while the sensitivity of smooth muscle in NCR and WKR was similar to that of SHR. Angiotensin I induced contractions were inhibited by saralasin and by captopril, indicating presence of functionally active converting enzyme in the this vascular tissue. The local concentration of AT II formed from AT I, was evaluated based on AT II dose response curves and AT I response magnitude. The AT II formation was essentially similar in SHR, WKR and NCR and slightly enhanced in RHR. Inhibition of AT II formation with captopril and/or blockade of AT II receptors with saralasin failed to alter the spontaneous myogenic activity of the portal vein. Captopril reduced smooth muscle activity only in concentration several orders of magnitude greater than that needed to inhibit ACE. The concentration of captopril needed to inhibit AT I responses was similar in all strains of rats. It is concluded that AT II is rapidly formed in the portal vein due to local conversion of AT I. In the RHR portal vein the extent of AT I conversion is increased and the tissue sensitivity to AT II is decreased possibly due to mechanisms involved in the development of renovascular hypertension.
Angiotensin I↗
Neuroeffector function of isolated portal vein from spontaneously hypertensive and wistar-kyoto rats: dependence on external calcium concentration.
The calcium dependence of the vascular neuroeffector function has been studied in the portal vein of spontaneously hypertensive Okamoto rats (SHR) and Wistar-Kyoto rats (WKY). The noradrenaline (NA) sensitivity of veins of both species, expressed in terms of ED50, was decreased to the same extent in relation to the reduction in Ca2+ ion concentration below 2.5 mM. The responses to individual NA concentrations at subnormal Ca2+ concentrations were better maintained, however, in portal veins from SHR than from WKY, indicating that the excitation contraction coupling mechanism is less dependent on external Ca2+ concentrations in the portal vein from SHR than from WKY. In both strains of rats the spontaneous myogenic activity of the vessel was depressed in low Ca2+ concentrations to a greater extent than responses to nerve stimulation, which, in turn, were more reduced than the excitatory responses to exogenous NA or acetylcholine (ACh). Transmitter release (fractional overflow of 3H-NA/impulse) was less dependent on Ca2+ concentrations than the contractile nerve stimulation response. The persistence of all responses in reduced Ca2+ concentrations was significantly greater in the portal vein of SHR. It is concluded that the phasic, spontaneously active smooth muscle of the rat portal vein is highly dependent on the external calcium concentration and that various induced responses persist to a varying degree in reduced Ca2+ concentrations. It is suggested that this is due to interference with electromechanical coupling as well as myogenic spread of activation. Induced responses of the portal vein from SHR are, in general, less affected by decreased Ca2+ concentrations than the WKY portal vein, indicating an altered vascular smooth muscle excitation-contraction coupling mechanism in spontaneous hypertension. Possibly an increased efficiency of the coupling mechanism may contribute to augment vascular responses in the development of hypertension and promote structural vascular changes.
Animals↗
Contractile patterns of isolated oviductal smooth muscle under different hormonal conditions.
The isthmic portion of the human fallopian tube was excised during surgery and the ampullary-isthmic junction was identified. Muscle strips (1-mm wide) were dissected from the outer longitudinal and the inner circular layers at this region and used for isometric recordings of spontaneous contractile activity in organ bath experiments. It was found that the amplitude and the duration of individual contractions were similar during various phases of normal menstrual cycles, whereas the frequency of contractions was significantly increased during the periovulatory period in both circular and longitudinal muscle. During early pregnancy or treatment with combined oral contraceptives the motility pattern was similar to that observed in the late luteal phase, being characterized by a comparatively low contraction frequency. In the perimenopausal period, irregular patterns were frequently observed whereas preparations obtained from postmenopausal women exhibited a very weak activity with low amplitude and frequency of contractions. Similar activity was encountered in specimens from patients treated with androgens. It is concluded that endogenous estrogens stimulate human oviductal contractility while endogenous progesterone has a depressive action on tubal activity. Both effects occur with a certain delay and are prolonged for up to 3 days, i.e., the changes in the serum levels of ovarian steroids and the induced alterations of tubal contractility are out of phase.
Adult↗
Distensibility of the left atrial wall in spontaneously hypertensive rats compared with that in normotensive Wistar-Kyoto rats.
1. The cardiac mechanoreceptors, which in rats are mainly located in the left atrial wall, are reset in spontaneously hypertensive rats. The atrial pressure has to be almost twice as high in spontaneously hypertensive rats as in normotensive controls to produce similar receptors activations, as is apparent from previous studies. 2. The present study was performed to investigate whether this resetting is due to decreased distensibility of left atrial walls in the spontaneously hypertensive rats. 3. Static load-length relationships were investigated in vitro on left atrial strips, and pressure-volume relationships were studied on isolated left atria from spontaneously hypertensive and normotensive Wistar-Kyoto rats. 4. The force per cross-sectional area exerted during a relative length increase of 80% was significantly greater in spontaneously hypertensive rats. The dynamic but not in the static distensibility was significantly lower in these animals. 5. The decreased dynamic distensibility of left atrial walls in spontaneously hypertensive rats can at least partly explain the resetting of atrial receptor function.
Animals↗
Pre- and postjunctional beta-adrenoceptor mediated effects on transmitter release and effector response in the isolated rat portal vein.
Pre- and postjunctional control mechanisms of the portal vein of spontaneously hypertensive rats (SHR) were characterized. Emphasis was placed on the influence of the presynaptic beta-adrenoceptor mediated mechanism for regulation of neuronal noradrenaline (NA) release (studied as tritium overflow) and its consequences for the contractile response under in vitro conditions. It was found that isoprenaline increased, whereas dl-propranolol decreased the release of neuronal NA during transmural nerve stimulation, while effector responses remained unaltered. d-Propranolol and the beta-1 selective adrenoceptor antagonist, metoprolol, did not affect these two variables. It is concluded that the presynaptic beta-adrenoceptors in the rat portal vein are mainly of the beta-2 type and mediate facilitation of neuronal transmitter release and that concomitant changes of the effector responses of this tissue are below the level of detection under the present experimental conditions.
Animals↗
Dissociation of electrical and mechanical activity caused by vibrations in the spontaneously active smooth muscle of the rat portal vein.
The effects of vibrations on the electrical membrane discharge and on the contractile force of the spontaneously active smooth muscle of isolated rat portal vein were studied. The electrical activity was recorded extracellularly and quantitatively related to the mean active force. Sinusoidal vibrations (40 Hz, 2.5--3.0% tissue length peak to peak), applied in the longitudinal direction of the smooth muscle, caused prompt and reversible reduction of active force but neither the pattern of the phasic contractions nor the electrical membrane discharge was altered. The degree of inhibition of mechanical activity increased with vibration amplitude, activity being 50% of control at a vibration amplitude of 12 +/- 4% (mean +/- S.D., n = 8). It is concluded that the induced length changes caused prompt dissociation between electrical membrane discharge and mechanical force development in the vascular smooth muscle. This finding adds support to the previously forwarded hypothesis that vibrations cause inhibition of contracting muscle by direct action on the contractile process.
Animals↗
Distensibility of left atrium in normotensive and spontaneously hypertensive rats.
In spontaneously hypertensive rats (SHR) left atrial mechanoreceptors are reset. Thus, left atrial pressure must be almost twice as high in SHR as in normotensive rats to produce comparable degrees of receptor activation and reflex sympathetic inhibition. The present study was performed to investigate whether this resetting is due to a decreased atrial distensibility in SHR. Static load-length relationships were therefore investigated on isolated left atrial strips from 11 pairs of male SHR and Wistar Kyoto rats (WKR). After each experiment the strips were fixed at a passive tension of 4 mN and the average wall thickness was determined histologically. Furthermore, pressure-volume relationships were studied on non-beating, isolated left atria from SHR and WKR. Distensibility was here defined as % volume increase when LAP was increased from 2.5 to 12.5 mmHg either rapidly (0.5--1 s, "dynamic" distension) or slowly (3 min, "static" distension). Atrial wall thickness did not differ significantly in SHR and WKR, but the passive force (mN) per cross sectional area exerted during elongation above 80% was greater (P less than 0.05) in SHR. Also the "dynamic", but not the "static" volume distensibility was significantly lower in SHR (P less than 0.01). The decreased dynamic distensibility of SHR left atrial walls can at least partly explain the resetting of the atrial receptors activated during the rapid filling phase.
Animals↗
Contractile and morphological properties of the portal vein in spontaneously hypertensive and wistar-kyoto rats.
In perfusion experiments, previous investigations have shown an increased responsiveness of isolated vascular beds from spontaneously hypertensive rats (SHRs) compared with Wistar-Kyoto controls (WKYs). The results have suggested that there are differences in the arterial vessels but not in the venous vessels. Here we have tested the latter part of this hypothesis by comparing the contractile and morphological properties of isolated portal veins from 18 SHRs and 18 WKYs, all 3-4 months old. We found no differences between these veins as regards: (a) maximum force response; (b) active and passive force--length relationship; (c) sensitivity to exogenous noradrenaline without and with inhibition of neuronal uptake by cocaine, and (d) cross-sectional area of the longitudinal smooth muscle layer. There was, however, evidence for difference at the cellular level, for the active force per unit cell area was 17% lower in the SHR vessels compared with that in the WKY vessels. With this exception, the results indicate that the morphological and functional differences which have been reported by others for arterial vessels from SHRs and WKYs do not prevail in the portal vein taken from rats at 3-4 months of age.
Animals↗
Evaluation of unilateral kidney function in children. A comparison between renography and separate clearance.
Unilateral kidney function in children was evaluated by determination of 51Cr-EDTA-clearance combined with estimation of side distribution of kidney function by renography. As reference, separate clearance of 51Cr-EDTA, determined by sequential external ureteral occlusions on both sides, was used. A comparison between these two methods was made in 28 patients with varying degrees of unilateral kidney function impairment. A significant correlation was found when the renograms were corrected for extrarenal background activity. Thus, renography in combination with determination of the glomerular filtration rate with 51Cr-EDTA is a valuable method for evaluating separate kidney function in children, both methods being easily performed and requiring small radiation doses.
Adolescent↗
Effects of metoprolol on adrenergic mechanisms during long- and short-term antihypertensive treatment of spontaneously hypertensive rats.
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Animals↗
Adrenergic and novel non-adrenergic neuronal mechanisms in the control of smooth muscle activity in the human oviduct.
The isthmic portion of human Fallopian tubes was excised during surgery and the ampullary-isthmic junction was identified. The external, longitudinal and the inner, circular muscle layers of this structure were then mechanically separated. The contractile activity of thin strips from these layers was studied isometrically in organ bath experiments. Administration of various adrenoceptor agonists and antagonists revealed that the responses of the longitudinal smooth muscle are primarily mediated by alpha-adrenoceptors while there is a marked dominance of beta-adrenoceptor-mediated effects in the circular layer. Transmural nerve stimulation to those caused by exogenous noradrenaline, although nerve-mediated inhibition of circular muscle activity was not abolished entirely by propranolol, atropine or guanethidine, but by tetradotoxine, indicating the existence of a hitherto unknown non-adrenergic, non-cholinergic, inhibitory neurogenic mechanism. The results support the concept of a specific sphincter-like function controlling ovum transport at the human oviductal isthmus, and that this sphincter may be controlled by both adrenergic nerves and nerves liberating an unidentified transmitter substance.
Adult↗
Structural and functional ontogenetic development of the rat portal vein after neonatal 6-hydroxydopamine treatment.
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Adrenergic Fibers↗
Effects of Tris on vascular smooth muscle.
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Animals↗
Increased noradrenaline release in rat portal vein during sympathetic nerve stimulation due to activation of presynaptic beta-adrenoceptors by noradrenaline and adrenaline.
With the aim of investigating whether exogenous noradrenaline (NA) and adrenaline (A) can modulate transmitter release via the stimulation of presynaptic beta-adrenoceptors, 3H-release from isolated portal veins was studied after pretreatment with 3H-1-NA, phenoxybenzamine, desipramine and normetanephrine. NA (10 muM) and A (0.05 muM) increased the fractional 3H-release elicited by sympathetic nerve stimulation by 30%. This effect could be blocked by d, 1-propranolol which per se reduced the release by 10%. It is concluded that NA can facilitate its own release via a presynaptic beta-adrenoceptor-mediated positive feed-back mechanism and that adrenaline can stimulate this beta-adrenoceptor-mediated mechanism.
Animals↗
Inhibitory effects of vibrations on contractility of isolated rabbit papillary muscle.
The effects of vibrations on myocardial contractility have been tested in isolated rabbit papillary muscles. Sinusoidal longitudinal oscillations were found to inhibit active force in the paced preparation to an extent which depended on vibration amplitude and frequency. The inhibitory effect of vibrations on myocardial contraction resembled that previously seen in other types of muscle. Vibration during the inactive phase did not alter passive muscle tension. When the vibrator was controlled by phonocardiographic recordings from a normal subject or from patients with congenital aortic stenosis, pronounced inhibition was obtained only by vibrations corresponding to a systolic murmur. It is concluded that the myocardium is sensitive to oscillating length changes. If the ventricular muscle in vivo is exposed to vibrations during systole the cardiac function might be seriously interfered with.
Animals↗
Neuroeffector maturity of portal veins from newborn rats, rabbits, cats and guinea pigs.
Isolated portal veins from newborn and adult rats, rabbits, cats and guinea pigs were studied isometrically. Spontaneous activity and induced responses to transmural nerve stimulation (NS), noradrenaline, tyramine, acetylcholine and BaCl2 were quantitated. In agreement with our previous observations the portal veins of the newborn rat was found to lack spontaneous activity and responsiveness to applied stimuli whereas the newborn rabbit's portal vein showed inconsistent and weak responses. In the neonatal cat and guinea pig portal veins the pattern of the spontaneous activity and induced responses resembled those found in vessels from adult animals. It is concluded that the portal vein maturity at birth in several respects dramatic neuroeffector development of the portal vein during the postnatal period in the rat corresponds to prenatal events in cats and guinea pigs which are more highly developed at birth. Consequently, the lack of responsiveness of the portal vein during the first week of life does not seem to be secondary to the hormonal and hemodynamic adjustments during the neonatal period. Rather, the postnatal development of the rat portal vein occurs according to a genetically predetermined schedule, possible in parallel with the ontogenesis of vascular control in general.
Acetylcholine↗
Reduced adrenal amine synthesis in spontaneously hypertensive rats after long-term treatment with propranolol.
Male spontaneously hypertensive rats were either fed a diet containing 3 mg/g of (+/-)-propranolol, giving a mean daily intake of 178 +/- 4.2 mg/kg, or a control diet from 7 weeks of age for 6 months. Three days after cessation of propranolol-treatment, the arterial blood pressure of the treated group was about 10% lower than that of the control group. Adrenal dopamine content and tyrosine hydroxylase activity were reduced to 76% and 71% of the control values, respectively. The results indicate that propranolol causes a reduced sympathetic discharge through its central action, although blockade of beta-adrenoceptor-mediated local regulatory mechanisms cannot be excluded.
Adrenal Glands↗