Search PubMed⌕ Search

Biomedical subjects

M G Collis

Publications and source records attributed to M G Collis.

At least 55 records · Page 3Linked to original sources
PubMed1980

Antidepressant drug action and presynaptic alpha-receptors.

Receptors have been demonstrated on the terminations of the sympathetic adrenergic nerves. One type, the so-called alpha 2-receptors, are activated by the norepinephrine that is released from the nerve terminals into the synaptic cleft; this activation causes a reduction in the output of the transmitter (negative feedback). Recent studies have demonstrated that certain antidepressant drugs can block these alpha 2-receptors and thus prevent their inhibitory action on the release of norepinephrine. If this occurs in the brain, the increases in norepinephrine levels could help explain the antidepressant action of these agents.

Animals↗
PubMed1980

Interaction of the tricyclic antidepressant amitriptyline with prejunctional alpha and muscarinic receptors in the dog saphenous vein.

Amitriptyline can cause tachycardia and arrhythmia associated with an excessive release of cardiac catecholamines. We have investigated its effects on norepinephrine release from adrenergic nerves by using the dog saphenous vein as a model of the sympathetic neuroeffector junction. Isolated strips of vein were mounted for isometric tension recording or incubated with [3H]norepinephrine and mounted for superfusion, tension recording and the superfusate. Amitriptyline (10(-6); 5 x 10(-6) M) increased the overflow of [3H]norepinephrine but decreased that of [3,4-3H]dihydroxyphenylglycol from electrically stimulated strips. The selective decreased in the overflow of this metabolite indicates that amitriptyline inhibits neuronal uptake. However, the increased overflow of [3H]norepinephrine caused by amitriptyline also occurred when neuronal uptake was blocked by cocaine (3 x 10(-5) M) but was abolished when prejunctional alpha receptors were blockade by phentolamine (10(-5) M). Amitriptyline attenuated the prejunctional inhibitory action of exogenous norepinephrine, this indicates that the drug interacts with prejunctional alpha receptors. Amitriptyline also antagonized the prejunctional inhibitory action of acetylcholine, both in the absence and presence of cocaine and phentolamine. These effects were not due to a nonspecific action of the drug as it did not reduce the prejunctional inhibitory effect of histamine. Thus, amitriptyline can increase the concentration of norepinephrine at the neuroeffector junction by blockade of neuronal uptake and by interacting with prejunctional alpha and muscarinic receptors. Since the cardiac adrenergic nerves also possess these receptors, the results could help to explain the cardiotoxic effects of the drug.

Amitriptyline↗
PubMed1979

Enhanced release of noradrenaline in the kidney of the young spontaneously hypertensive rat.

1. Vascular reactivity and noradrenaline overflow were studied in Tyrode solution-perfused kidneys from young (6 weeks) normotensive and spontaneously hypertensive (SH) rats. 2. The vasoconstrictor response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats. 3. Nerve stimulation evoked a greater release of noradrenaline in the kidneys from young SH rats than in those from normotensive animals. 4. The results demonstrate that the renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension.

Animals↗
PubMed1978

Neuronal and vascular reactivity in isolated perfused kidneys during the development of spontaneous hypertension.

1. Vascular reactivity was studied in Tyrode solution perfused kidneys from young (7 weeks) and mature (4-6 months) spontaneously hypertensive rats (SH rats). 2. The response to nerve stimulation was greater in the kidneys from young SH rats than in those from young control rats, both in control solution and after inhibition of the disposition of noradrenaline; both groups exhibited the same sensitivity to noradrenaline, angiotensin II and barium chloride. 3. The response to nerve stimulation was normal in kidneys from mature SH rats, but responses to noradrenaline, angiotensin II and barium chloride were greater than the control. 4. Cocaine potentiated the response to nerve stimulation more in the kidneys from mature SH rats than in those from the control rats. 5. The results suggest that renal sympathetic nerves release more noradrenaline than normal in the young SH rats, which could be an important factor in causing hypertension. 6. In the established phase of spontaneous hypertension the vascular reactivity to exogenous agonists is increased, probably as a consequence of high blood pressure; the more efficient neuronal uptake causes normalization of the response to sympathetic nerve stimulation.

Angiotensin II↗
PubMed1978

Increased renal vascular reactivity to angiotensin II but not to nerve stimulation or exogenous norepinephrine in renal hypertensive rats.

We isolated and perfused both the "clipped" and "contralateral" kidneys from Goldblatt renal hypertensive and sham-operated control rats, 1--104 days postoperatively. Responses to renal nerve stimulation were depressed in clipped kidneys from hypertensive rats (1 day postoperative), and these kidneys were supersensitive to exogenous norepinephrine (1--31 day) when compared with the contralateral organ of the same animal. Similar alterations were found between clipped and contralateral kidneys from sham-operated control rats. There was no difference in responses to renal nerve stimulation of norepinephrine between clipped kidneys from hypertensive and control rats, but clipped kidneys from hypertensive rats were supersensitive to angiotensin II (17 and 31 days). Comparison of contralateral kidneys from hypertensive and control rats revealed no change in norepinephrine sensitivity or in responses to renal nerve stimulation, but there was a reduction in the slope of the dose-response curve to norepinephrine and of the maximal effect of the catecholamine (104 days) and a pronounced supersensitivity to angiotensin II (17--104 days) in the hypertensive rats. These results indicate that (1) renal nerve function and norepinephrine sensitivity of the isolated renal vasculature are unchanged in renal hypertension, but clipping partially denervates the kidney causing depressed nerve function and unilateral norepinephrine supersensitivity, unrelated to hypertension; (2) the prolonged high pressure load on the contralateral kidney may impair the function of the vascular smooth muscle; and (3) bilateral supersensitivity to angiotensin II is associated with hypertension but is not solely a consequence of the high pressure.

Angiotensin II↗
PubMed1976

The renin-angiotensin system, dietary salt, and increased sensitivity to noradrenaline in mesenteric vasculature preparations from renal/salt hypertensive rats.

Exogenous angiotensin II causes noradrenaline supersensitivity in rat mesenteric vasculature preparations. The noradrenaline supersensitivity of tissues from renal/salt hypertensive rats, with low plasma renin activity, is not caused by endogenous angiotensin II since it was unaffected by Sar1 Ileu8 angiotensin II. Dietary salt-loading caused a small increase in noradrenaline sensitivity.

Angiotensin II↗
PubMed1975

Vascular reactivity to noradrenaline, potassium chloride, and angiotensin II in the rat perfused mesenteric vasculature preparation, during the development of renal hypertension.

The degree of reactivity to noradrenaline of the perfused mesenteric vasculature and the blood pressure of the renal hypertensive rat were correlated. Early (true) supersensitivity was demonstrated for noradrenaline and angiotensin but not for KCl. Later (apparent) hyperreactivity to all three substances was related to an elevated maximal response. The potentiating actions of endogenous angiotensin could cause the early (true) supersensitivity to noradrenaline.

Angiotensin II↗
PubMedDate not supplied

Tachyphylaxis to 5-hydroxytryptamine in perfused kidneys from spontaneously hypertensive and normotensive rats.

Isolated perfused kidneys from 4- to 6-month-old spontaneously hypertensive rats (SHR, Japanese strain) exhibit increased "vascular reactivity" to 5-hydroxytryptamine (5-HT) and a slower rate of development of tachyphylaxis to this substance when compared with kidneys from normotensive Wistar-Kyoto (WKY) rats. We investigated the possibility that the reduced rate of development of tachyphylaxis could be related to a interaction of 5-HT with adrenergic mechanisms or with endogenous 5-HT. Tachyphylaxis was induced by repeated administration of 5-HT to kidneys from SHR and WKY rats. This procedure did not affect vasoconstrictor responses evoked by norepinephrine. The development of tachypylaxis to 5-HT in kidneys from SHR and WKY rats was not changed by chemical sympathectomy with 6-hydroxydopamine. Treatment of SHR with para-chlorophenylalanine did not affect their blood pressure or the development of tachyphylaxis to 5-HT. These results indicate that delayed tachyphylaxis to 5-HT in kidneys of SHR is not due to an interference with adrenergic mechanisms and does not depend on endogenous 5-HT levels. The phenomenon represents an unusual modification of vascular smooth muscle exposed to chronic high pressure, but it is unlikely that the vasoconstrictor effects of 5-HT contribute to the maintenance of hypertension in the SHR.

Animals↗
PubMedDate not supplied

Renal vascular reactivity in the young spontaneously hypertensive rat.

The renal resistance vessels of the mature spontaneously hypertensive rat (SHR) exhibit increased reactivity to vasoconstrictor agonists. This could be a cause or consequence of hypertension. We have compared vascular reactivity in isolated perfused kidneys from 46-day-old SHR and from normotensive control rats. The amplitude of responses in kidneys from the SHR to angiotensin II, barium chloride, or norepinephrine was not different from the control. Therefore, increased reactivity of the renal vascular smooth muscle cannot be an early pathogenic mechanism in spontaneous hypertension. Responses evoked by 5-hydroxytryptamine (serotonin) were of a greater amplitude in the SHR than in the control kidney. However, this difference was due to an interaction of serotonin with the sympathetic nerves, as it was abolished by treatment of the rats with 6-hydroxydopamine. Responses induced by electrical stimulation of the renal sympathetic nerves were also of greater amplitude in SHR than in control kidneys, both before and after the blockade of norepinephrine disposition mechanisms. Nerve stimulation evoked a greater efflux of endogenous norepinephrine from kidneys of the SHR than from those of control rats. Thus, the increased reactivity of the SHR kidney to renal nerve stimulation is due to an augmented release of endogenous norepinephrine. This could be an important factor in the early development of hypertension.

5-Hydroxytryptophan↗
PubMedDate not supplied

Decreased release of norepinephrine in the isolated kidney of the adult spontaneously hypertensive rat.

Renal resistance vessels of the mature spontaneously hypertensive rat (SHR) exhibit an increased reactivity to exogenous norepinephrine, but a normal response to renal nerve stimulation. This difference could be due either to depression of the exocytotic process or to accelerated disposition of the released transmitter. We compared the overflow of norepinephrine in isolated perfused kidneys from adult SHR and normotensive rats. After previous incubation with 3H-norepinephrine, renal nerve stimulation caused smaller increases in the overflow of intact tritiated transmitter and its metabolites in kidneys form SHR than in those from normotensive controls. A similar difference was found when the amounts of endogenous norepinephrine were measured radioenzymatically. The tissue content of norepinephrine was comparable in kidneys from both hypertensive and normotensive animals. The uptake of 3H-norepinephrine was comparable in kidneys from SHR and normotensive controls; cocaine caused a comparable depression of the 3H-uptake in which then explains the normal vasoconstrictor response to renal nerve stimulation despite the increased responsiveness of the vascular smooth muscle cells to norepinephrine.

Adrenergic Fibers↗
PubMedDate not supplied

Hypotensive action of captopril in spontaneously hypertensive and normotensive rats. Interference with neurogenic vasoconstriction.

The effects of captopril and angiotensin II on adrenergic neurotransmission have been studied in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). In a pithed rat preparation, vasoconstrictor responses evoked by spinal stimulation were greater in SHR than WKY (p less than 0.01). Captopril reduced responses to electrical stimulation and this reduction was greater in the SHR (p less than 0.001). Bilateral nephrectomy reduced the vasoconstrictor responses to nerve stimulation in both strains of rat and abolished the effects of captopril. In an isolated perfused mesenteric artery WKY (p less than 0.05). Angiotensin II potentiated responses from both strains of rat, however the amplitude of the potentiation was greater in preparations from the SHR than those from WKY (p less than 0.002). Captopril (30 mg/kg by mouth) reduced blood pressure in conscious SHR over a 5-day dosing period. In WKY rats, no hypertensive action of captopril was observed. However, in another normotensive strain, the Alderley Park Wistar rat (APW), captopril lowered blood pressure. Plasma renin activity was not significantly different among these three strains of rat. The APW have previously been shown to be very sensitive to the adrenergic potentiating actions of angiotensin II. Captopril thus lowers blood pressure in SHR and APW, and both these strains are sensitive to the adrenergic potentiating actions of angiotensin II. It does not lower blood pressure in WKY, which is relatively insensitive to these actions of the octapeptide. Therefore, the hypotensive action of captopril in the rat may be due to its interference with the adrenergic potentiating effect of angiotensin II.

Adrenergic Fibers↗