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Biomedical subjects

N J Rusch

Publications and source records attributed to N J Rusch.

At least 55 records · Page 3Linked to original sources
PubMed1989

Calcium channel alterations in genetic hypertension.

We proposed earlier that voltage-dependent calcium (Ca2+) current is altered in single azygos venous cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). In this study, the effects of different intracellular concentrations of ethylene glycol-bis-N,N,N',N',-tetraacetic acid (EGTA) on Ca2+ currents were investigated. Vascular muscle cells from SHR and WKY rats were equilibrated with pipette solution containing 0.1 mM or 10 mM EGTA. Increasing the EGTA concentration from 0.1 to 10 mM in SHR vascular cells significantly enhanced the peak amplitude of the longer lasting (L) current from 87 +/- 12 pA to 152 +/- 8 pA, while the transient (T) current amplitude was not significantly different (52 +/- 7 pA and 36 +/- 7 pA, respectively). In WKY rat vascular muscle cells, the amplitudes of the T and L currents were not significantly different with the same comparison of intracellular EGTA concentrations. These observations suggest that relatively low intracellular Ca2+ concentrations can more strongly modulate Ca2+ current through the L channel in SHR than WKY rat vascular muscle cells.

Animals↗
PubMed1989

Regional variation of postjunctional alpha-adrenoceptor responses in the developing renal vascular bed of sheep.

Postjunctional alpha 1- and alpha 2-adrenoceptor vasoconstrictor responses were evaluated in isolated segments of main renal artery, segmental renal artery, and renal vein from fetal (130-138 d of gestation; term 145 d), newborn (3-15 d age), and nonpregnant adult sheep. Vascular rings were mounted at their optimal resting tension and responses to phenylephrine (alpha 1-adrenoceptor agonist) and guanabenz and UK14304 (both alpha 2-adrenoceptor agonists) were determined. Optimal resting tension increases with development in the main renal artery, segmental renal artery, and renal vein of sheep. Arterial vessels develop more isometric tension to alpha 1-adrenoceptor stimulation than to alpha 2-adrenoceptor stimulation, whereas venous segments develop similar isometric tension to alpha 1- and alpha 2-adrenoceptor stimulation. The segmental renal artery develops more isometric tension to alpha 2-adrenoceptor stimulation than the main renal artery. No large developmental differences exist among vessels in the sensitivity (concentration required for half maximal response, ED50) to alpha-adrenoceptor stimulation except for the renal vein with alpha 2-adrenoceptor stimulation. Maximum isometric tension corrected for vessel cross-sectional area decreases with age for all vessels with both alpha 1- and alpha 2-adrenoceptor stimulation. These findings may reflect developmental differences in receptor number and affinity or differences in vascular smooth muscle function. In addition, these data suggest that whereas both alpha 1- and alpha 2-adrenoceptors mediate vasoconstriction in the renal circulation, they may do so at different sites.

Age Factors↗
PubMed1988

Calcium currents are altered in the vascular muscle cell membrane of spontaneously hypertensive rats.

Calcium currents were recorded during whole-cell voltage clamp in cultured azygos venous muscle cells from 1-3-day-old normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Different holding potentials were used to separate total cell current into its transient (T) and sustained or long-lasting (L) components. In recordings from 30 WKY and 30 SHR vascular cells, total cell calcium current was the same between cells from normotensive (167 +/- 20 pA) and hypertensive (139 +/- 15 pA) rats. However, the relative proportion of T and L calcium currents was different between WKY and SHR cells. In WKY cells, the peak amplitude of the L current was less than that of the T current (42 +/- 30% of total current), whereas in SHR cells, the L current was greater (62 +/- 3% of total current). Calcium currents in vascular muscle cells from SHR were activated and inactivated at more positive potentials than in cells from WKY. This study directly compares transmembrane calcium current in isolated cells from WKY and SHR blood vessels and shows that the proportions of T and L calcium channels activated by depolarization are altered in this genetic model of hypertension.

Animals↗
PubMed1988

The effect of cold on adrenergic neurotransmission in canine saphenous arteries and veins.

The effect of severe cold (5 to 10 degrees C) on adrenergic neurotransmission was compared in the isolated cutaneous (saphenous) artery and vein of the dog. The vein contracted to sympathetic nerve stimulation at temperatures as low as 10 degrees C; higher temperatures were needed for the artery to contract. Both blood vessels contracted to exogenous norepinephrine at temperatures as low as 5 degrees C. However, the contractile response to exogenous norepinephrine was less in the saphenous artery, and contractions to high K+ solution were depressed by cooling more in the artery than in the vein. During electrical stimulation of the sympathetic nerves in saphenous arteries and veins previously incubated with labeled norepinephrine, progressive cooling from 37 to 5 degrees C caused a sharp decline in overflow of [3H]norepinephrine and its metabolites. However, overflow of labeled norepinephrine in both blood vessels continued at very cold temperatures. Thus the inability of the saphenous artery to contract to sympathetic nerve stimulation at 10 degrees C can be explained by a greater sensitivity of the arterial smooth muscle to the direct depressant effect of cold, rather than to a differential release or metabolism or norepinephrine in the arterial wall or a loss of responsiveness to norepinephrine at very cold temperatures.

Animals↗
PubMed1988

Nitrendipine inhibition of calcium current in rat vascular muscle cells.

The effect of nitrendipine on spontaneous contraction frequency and Ca2+ currents was studied in spontaneously active rat azygos venous cells in primary culture. Nitrendipine reduced the frequency of contraction in a concentration-dependent manner, with 50% inhibition (IC50) at approximately 10(-7) M. In similar cells using the whole-cell voltage-clamp technique, nitrendipine (10(-7) M) reduced the peak magnitude of the longer lasting, high-threshold (L) Ca2+ channel current by 52 +/- 6%, while the transient, low-threshold (T) Ca2+ channel current was unaffected. As estimated from the current-voltage inactivation relationship, the dissociation constant (Kd) for nitrendipine binding to the resting state of Ca2+ channels was 108 nM for the L channel and greater than 2 microM for the T channel. This high-affinity binding of the dihydropyridine to the resting state of the L channel in vascular muscle contrasts with the lower-affinity binding reported in cardiac muscle. Thus, nitrendipine may inhibit spontaneous activity in vascular muscle cells at least partly by blocking Ca2+ current through L channels.

Animals↗
PubMed1987

Felodipine actions on vascular muscle Ca2+ channels.

Felodipine is a potent, but relatively slow, relaxation agent in rat caudal artery, decreasing 30 mM K+ contractions by 39% at a concentration of 1 nM and 88% at 10 nM. Membrane potential at rest was unchanged, but 10 nM felodipine caused a 5 mV hyperpolarization of vascular muscle cells previously depolarized by 30 mM K+. Felodipine selectively decreased the sustained, but not the transient, type of calcium current in a whole-cell voltage clamp of azygos venous muscle cells. Relaxation by felodipine was additive to that caused by 10 microM trifluoperazine, a calmodulin antagonist, arguing against an action of felodipine via calmodulin. The vascular muscle relaxant effects of felodipine appear to be explainable by blockade of the sustained type of calcium channels.

Animals↗
PubMed1986

Differential reactivity to 5-hydroxytryptamine in canine coronary arteries.

Responses to 5-hydroxytryptamine (5HT) were compared in large [2.1-3.0 mm outside diameter (OD)], medium (1.5-1.8 mm OD) and small (0.5-1.0 mm OD) isolated canine coronary arteries. 5HT produced contraction of large and medium arteries, with the maximal response averaging 35.1 +/- 4.0 and 21.0 +/- 3.3%, respectively, of the contraction to 100 mM KCl. Endothelial removal increased the response to 5HT, with the maximal response averaging 43.6 +/- 12.6 and 32.4 +/- 7.5%, respectively, of the 100 mM KCl contraction. Small arteries did not contract significantly to 5HT in the presence or absence of endothelium. However, 5HT (10(-6) M) contracted small arteries that were contracted with 30 mM KCl, averaging 130 +/- 3% of the original contraction to KCl. This further contraction to 5HT was slightly potentiated by removal of the endothelium. We conclude that, unlike larger epicardial arteries, coronary arteries less than 1 mm OD are unresponsive to 5HT under resting conditions. Failure of small arteries to contract to 5HT cannot be explained by an inhibitory influence of the endothelium. However, 5HT enhances the contraction of small arteries to K+, and this response tends to be augmented by endothelial removal.

Animals↗
PubMed1985

Vasopressin induced rhythmic activity in rat basilar artery.

The effects of vasopressin on membrane potential and tension were studied in isolated segments of basilar arteries from the University of Iowa colonies of normotensive inbred Kyoto-Wistar rats (WKY) and stroke-prone spontaneously hypertensive rats (SP-SHR). In the presence of vasopressin (0.01-0.3 IU/ml), basilar arteries from WKY, but not from SP-SHR, developed rhythmic contractions. These contractions were recorded in 13 of 14 WKY basilar arteries, were unaffected by pretreatment with 6-hydroxydopamine, and were characterized by 20-100 dyne oscillations in tension, occurring 1-3 cycles/min, and superimposed on the vasopressin-induced contraction (averaging 60 dynes at 0.01 IU/ml or 160 dynes at 0.3 IU/ml). However, resting membrane potentials were not different in SP-SHR vs. WKY at 37 degrees C, and both strains showed about the same (11 mV) depolarization by 0.1 IU/ml of vasopressin. The rhythmic contractions were enhanced by K+-free solution, and abolished in the presence of high K+ solution (30 mM), suggesting that active Na+-K+ transport may be involved in modulating the rhythmic activity. These findings are consistent with the hypothesis that the vasopressin-induced rhythmic contractions in WKY basilar arteries are at least partly dependent on a reduced activity of electrogenic Na+-K+ active transport in WKY as compared to SP-SHR.

Animals↗
PubMed1984

Difference in vasopressin-induced contraction of basilar arteries from stroke-prone spontaneously-hypertensive rats (SP-SHR) and control Wistar-Kyoto rats (WKY).

Vasopressin (0.01-0.3 IU/ml) contracted isolated segments of rat basilar arteries from stroke-prone SHR (SP-SHR) and normotensive Wistar-Kyoto rats (WKY) unequally. Basilar arteries from SP-SHR were more responsive to vasopressin than were those from WKY when adrenergic nerve endings were present in both preparations. After destruction of adrenergic nerve endings by in vitro 6-hydroxydopamine treatment, the ED50 for vasopressin in both WKY and SP-SHR arteries decreased by a factor of three, indicating that the contractions caused by vasopressin were similarly modulated by prejunctional neurotransmitter release. However, only arteries from WKY showed prominent rhythmic relaxation-contraction cycles superimposed upon the vasopressin-induced tone. The tension cycles were 20-100 dyn in amplitude and occurred at 1-3 cycles/min. These tension oscillations of WKY were pronounced and obvious, sometimes amounting to as much tension as the underlying tonic contraction. Tension cycles could reflect a physiological contraction-relaxation phasing mechanism that fails to occur in basilar arteries of SP-SHR. The rhythmic activity was enhanced by K+-free solution and abolished by 30 mM K+ solution, suggesting that pacemaker changes in K+ conductance may underlie the WKY tension oscillations. It is suggested that the absence of rhythmic contractions in SP-SHR basilar arteries may be explained by greater activity of the electrogenic Na+-pump, which would tend to prevent the rhythmic oscillations in tension. These observations suggest that vasopressin has a differential action on basilar arteries of SP-SHR and WKY.

Adrenergic Fibers↗
PubMed1983

Effect of cold on the blood vessel wall.

The effect of cold has been studied on isolated canine and human blood vessels. These have led to the following conclusions concerning the phenomenon of the hunting reaction seen in human extremities on their exposure to severe cold. (1) On exposure to cold there is a marked increase in the affinity of the postjunctional alpha-adrenoceptors for norepinephrine. This results in a powerful constriction of the blood vessels and a cessation of blood flow to the distal tissue. As the temperature of the tissues rapidly falls, sympathetic nerve conduction is interrupted and vasodilatation occurs, due to the cessation of norepinephrine release and the depressor action of cold on the contractile machinery. The resultant return of blood flow rewarms the tissue, nerve conduction is reestablished, and this combined with the increased affinity of the alpha-adrenoceptors for norepinephrine leads to renewed vasoconstriction. Repetition of this cycle could result in the hunting reaction. (2) There appears to be a difference between the cutaneous artery and vein, in that the latter remains constricted at lower temperatures. (3) Preliminary experiments suggest that the response of the human cutaneous vein to cold is qualitatively similar to the dog vein, although some quantitative differences are present.

Animals↗
PubMed1981

The effect of profound cooling on adrenergic neurotransmission in canine cutaneous veins.

1. Experiments were performed to investigate how profound cooling affects adrenergic neurotransmission and vascular smooth muscle reactivity in isolated saphenous veins of the dog. 2. Cooling from 37 to 5 degrees C caused progressive depression of the contractile responses to high K+ solutions, illustrating the direct inhibitory effect of cooling on depolarization-induced contraction of the venous smooth muscle cells. 3. During prolonged cooling to 20, 15 and 10 degrees C, the contractile response to exogenous norepinephrine (10(-8)-10(-6) M) was augmented compared to that at 37 degrees C. At 5 degrees C responses up to 10(-7) M were also augmented, but those at higher concentrations were depressed. When veins contracted with 2 x 10(-6) M-norepinephrine were cooled to 20, 15, 10 and 5 degrees C, there was a further increase in tension; this increase slowly subsided to control values at 5 degrees C but was sustained at the other temperatures. 4. Cooling to 20 and 15 degrees C augmented the contraction caused by low but not high frequencies of electrical stimulation of the adrenergic nerve endings. Further cooling to 10 degrees C depressed, and at 5 degrees C abolished the response, demonstrating that profound cooling interrupted adrenergic neurotransmission. 5. In rings stimulated electrically at a low frequency (0.5 Hz), warming from 7 to 9 degrees C or from 9 to 11 degrees C, caused marked increases in tension. This may be explained by the combination of resumption of adrenergic neurotransmission and the increased responsiveness of the cutaneous venous smooth muscle cells to adrenaline. 6. The combination of enhanced affinity for noradrenaline combined with inhibition of neurotransmitter disposition probably permits the cutaneous veins to remain constricted during exposure to severe cold.

Animals↗
PubMed1981

Influence of sex difference and oral contraceptives on forearm reactive hyperemia.

Experiments were performed on normal male and female subjects to compare blood flow responses following release of an arterial occlusion (reactive hyperemia). Additionally, the effects of oral contraceptive therapy on the reactive hyperemia reaction were studied in female subjects. Forearm blood flow was measured with a strain-gauge plethysmograph, heart rate with an electrocardiograph, and mean arterial pressure was measured by auscultation. Blood flow was determined before and after circulatory arrest of 1, 3, and 5 min. Blood serum levels of 17 beta-estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were measured by radioimmunoassay. The mean resting forearm blood flow was similar in males and females (approximately 4 ml/100 ml/min). There were no significant changes in systemic mean arterial pressure or heart rate during the experiments. Following 1 min of arterial occlusion, the peak blood flow responses were similar in males and females. The peak blood flow responses following release of arterial occlusion were lower in males than in untreated females at occlusion intervals of 3 and 5 min. Females receiving oral contraceptives showed reduced peak blood flow responses after circulatory arrest of either 3 or 5 min as compared to untreated females. There were no significant differences in the recovery times of the hyperemic responses between males and females following any of the periods of occlusion. The peak blood flow responses following 3 min of arterial occlusion were significantly correlated with the blood serum levels of 17 beta-estradiol, LH and FSH, but not with the blood serum levels of progesterone. These results suggest that: (1) sex difference has a marked effect on the blood flow response following arterial occlusion, and (2) hormonal changes influence vascular responsiveness in the female.

Blood Pressure↗
PubMed1981

Prejunctional inhibition of norepinephrine release caused by acetylcholine in the human saphenous vein.

We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled with Krebs-Ringer solution. Acetylcholine depressed contractile responses to electric activation of the sympathetic nerve endings significantly more than those to exogenous norepinephrine; the relaxations caused by the cholinergic transmitter were antagonized by atropine. Helical strips were incubated with [3H]norepinephrine and mounted for superfusion. Electric stimulation augmented the fractional release of labeled norepinephrine. Acetylcholine caused a depression of the evoked 3H release which was antagonized by atropine but not by hexamethonium. These experiments demonstrate that, as in animal cutaneous veins, there are prejunctional inhibitory muscarinic receptors on the adrenergic nerve endings in the human saphenous vein. By contrast, the human vein also contains postjunctional inhibitory muscarinic receptors.

Acetylcholine↗
PubMed1981

Different behavior of the resistance vessels of the human calf and forearm during contralateral isometric exercise, mental stress, and abnormal respiratory movements.

Experiments were conducted in normal human volunteers to compare the response of the forearm and calf vessels to contralateral isometric exercise, mental stress, resisted breathing, coughing, and the Valsalva maneuver. Blood flows were measured by means of strain-gauge plethysmography, arterial blood pressure by auscultation, and heart rate by electrocardiography. Isometric exercise of one forearm (at one-third maximal voluntary contraction) for 90 seconds caused an increase in blood pressure and heart rate; the vascular resistance decreased in the resting forearm, and increased in the calf. The decrease in forearm resistance was greater with the subjects supine and attenuated with the subjects standing or reclining head-down. With arterial occlusion of the exercising forearm just prior to cessation of the handgrip, the blood pressure and the calf resistance remained elevated, while the heart rate returned to control. The forearm resistance increased during the occlusion period and remained elevated throughout it. Mental stress caused an increase in heart rate and blood pressure and a dilation of the forearm but not of the calf vessels; these changes were smaller in standing than in supine subjects. Resisted breathing and coughing caused an increase in heart rate and in forearm blood flow, but not in calf blood flow. The Valsalva maneuver was followed by decreases in blood flow to the upper and lower limbs. The different responses in forearm and calf vessels can be explained by a central component which triggers a vasodilator pathway (possibly cholinergic) which is distributed to forearm but not to calf vessels.

Adult↗