The rat isolated colon as a specific assay organ for angiotensin.

1. The antagonism of the contractile effects of prostaglandins F(2alpha) and E(2) by polyphloretin phosphate (PPP) was studied on the rat isolated colon.2. PPP (20 mug/ml) was found to reduce the myotropic action of angiotensin I (10 ng/ml) and II (0.3 ng/ml) whereas larger doses of both agents were not influenced.3. It is concluded that when a mixture of antagonists is used, including PPP, the rat isolated colon can be used to assay angiotensin with accuracy and specificity. The addition of 8-L-ala-AT(II) affords a further test of specificity.

Stimulating action of catecholamines on isolated preparations of the rat colon and human and rabbit taeniae coli.

1. Adrenaline and noradrenaline induced dose related relaxations of the superfused rat colon. The relaxations were progressively transformed into contractions when beta-adrenoceptors were blocked with increasing doses of oxprenolol.2. Since phentolamine or phenoxybenzamine inhibited the contractions induced by adrenaline or noradrenaline in the presence of oxprenolol, it is assumed that the contractions are caused by stimulation of excitatory alpha-adrenoceptors.3. Human and rabbit taeniae coli showed responses that were qualitatively similar to those observed with the rat colon.

Changes in plasma levels of vasopressin and renin in response to haemorrhage in dogs.

1. The rabbit rectum superfused with blood or Krebs solution was used to assay vasopressin in circulating blood and in plasma extracts respectively.2. Vasopressin was released by a rapid fall in diastolic pressure of as little as 5 mmHg, and the amount of vasopressin released was proportional to the magnitude of the fall in diastolic pressure in the range studied. These results would indicate that vasopressin release follows the magnitude of the fall in diastolic pressure more closely than the actual decrease in blood volume in haemorrhagic hypotension.3. It was shown that the time required to induce an increase in circulating vasopressin is inversely proportional to the severity of the fall in diastolic pressure; this suggested that the stimulation of neurosecretory reflex arc varies with the intensity of the stimulus.4. The slight changes in plasma renin activity as well as the pattern of renin release suggested the unlikeliness of the influence of renin upon vasopressin secretion under these circumstances. On the contrary, the results suggested that the secretion of large amounts of vasopressin tended to inhibit renin release.

Release of prostaglandins from the rabbit perfused kidney: effects of vasoconstrictors.

1 The rat stomach strip was used to assay prostaglandin E(2)-like material released by a rabbit isolated kidney perfused with Krebs solution.2 Doses of noradrenaline and angiotensin II producing similar vasoconstrictor effects released equivalent amounts of prostaglandins from the kidney.3 8-Leu-angiotensin II, a specific inhibitor of the natural octapeptide, blocked the action of angiotensin II on perfusion pressure and the release of prostaglandins, while the action of noradrenaline on both parameters was unaffected.4 Indomethacin, a specific inhibitor of prostaglandin biosynthesis, blocked the effects of both vasoconstrictors on prostaglandin release while their action on perfusion pressure was significantly enhanced.5 In the kidney effluent, amounts of prostaglandin E(2)-like material increased linearly with the rise in perfusion pressure induced by increasing doses of angiotensin II. These results indicate that prostaglandin output from the isolated kidney follows the rise in perfusion pressure.

Lithium-angiotensin interaction in rat neurohypophysis.

The effects of various concentrations of lithium upon basal and angiotensin-stimulated cyclic AMP accumulation were studied in isolated rat neurohypophysis. High doses of lithium diminished significantly the spontaneous accumulation of the nucleotide. This effect was not influenced by pre-incubation. Angiotensin-stimulated accumulation was inhibited by lithium at a dose which did not interfere with the basal accumulation of cyclic AMP. The possible physiological significance and mechanism of action are discussed.

Structural requirements for angiotensin analogues to accumulate cyclic AMP and release vasopressin from the incubated rat neurohypophysis.

1. Angiotensin I, a decapeptide, stimulated the accumulation of cyclic 3',5'-AMP (cyclic AMP) and the release of vasopressin from incubated rat neurohypophyses. 2. Various octapeptides related to angiotensin II were capable of producing similar neurohypophyseal effects. 3. Longer incubation periods were needed with peptides having alterations or omission (e.g. heptapeptide 2-8) at position 1 of the parent molecule to evoke similar effects to those of angiotensin II. 4. Our results suggest strongly that physiological doses of angiotensin-related molecules stimulate the secretion of vasopressin through cyclic AMP, and that the neurohypophyseal receptor responsible for these effects is similar to that involved in their peripheral actions.

Stimulation by angiotensin II of the release of vasopressin from incubated rat neurohypophyses---possible involvement of cyclic AMP.

1. Calcium did not influence the spontaneous release of vasopressin from rat neurohypophyses in vitro when used in concentrations of 0.05, 0.5 and 2.8 mM in the bathing medium. 2. Stimulation of the basal output of vasopressin by angiotensin II (1 X 10(-9) M) required at least 0.5 mM calcium in the medium. 3. Angiotensin II stimulated the release of vasopressin within 2.5 min of incubation, maximal release was observed after 10 min. 4. Angiotensin II rapidly promoted the accumulation of tissue cyclic AMP; maximal accumulation was observed after 5 min of incubation. 5. Theophylline and dibutyryl cyclic AMP produced varying degree of stimulation of the release of vasopressin. 6. Increases in vasopressin secretion and in the accumulation of cyclic AMP were always present when neurohypophyses were exposed to optiman concentrations of angiotensin II. The results presented suggested that cyclic AMP may be an intermediate step for the release of vasopressin by endogenous angiotensin II.

Excitatory effects of adrenaline upon isolated preparations of human colon.

The effect of beta-adrenergic blockade with oxprenolol upon adrenaline-induced relaxation of strips of human sigmoid colon was investigated. Following blockade of beta-adrenoceptors with oxprenolol, adrenaline evoked dose-dependent contractions of both longitudinal and circular muscle strips. Storage of the tissues for periods up to 24 hours at 4 degrees C did not modify the responses to adrenaline. Furthermore, the contractions induced by adrenaline following oxprenolol were significantly diminished by the addition of phentolamine, an alpha-adrenoceptor blocking agent. Our results would suggest that oxprenolol has the property of unmasking or revealing alpha receptors responsible for the excitatory effects of adrenaline upon isolated strips of human colon.

The influence of vesical distension on urethral resistance to flow: the collecting phase.

Using female dogs, changes in the urethral pressure profile in response to vesical distension were studied. It was noted that during the collecting phase there was an increase in the amplitude of the profile tracing. These experiments revealed that this increase is not mediated through an autonomic reflex and does not reflect a significant enhancement of alpha-adrenergic activity. These changes are mainly due to increased tension of the urethral muscle, secondly to detrusor stretch.

The influence of vesical distension on urethral resistance to flow: the expulsion phase.

The influence of vesical distension of the urethral pressure profile was studied in female dogs, using a model in which the bladder and urethra were separated. There was a reduction in the urethral resistance involving its smooth and striated muscle components. This reduction was completely blocked by ganglion blocking agents. Atropine did not influence these changes. Propranolol could only partially block this reflex. The other possible mechanisms that could be involved were discussed.

The influence of vesical distension on the urethral resistance to flow: a possible role for prostaglandins?

The possible role of prostaglandins in the mediation and/or modulation of the urethral response to vesical distension was investigated in female dogs. Three criteria for the possible involvement of these mediators have been investigated. Indomethacin could block the reduction of urethral resistance observed during vesical distension. Intra-arterial infusion of exogenous prostaglandin E2 resulted in a dose-dependent reduction in the urethral resistance to flow. Moreover, a significant release of prostaglandin E2 in the venous blood during the course of vesical distension could be demonstrated. The functional significance, mechanisms of release and mode of action of these highly active lipids are discussed.