A New Enzymatic Assay for Guanosine 3′:5′-Cyclic Monophosphate and Its Application to the Ductus Deferens of the Rat

Schultz, Günter; Hardman, Joel G.; Schultz, Karin; Davis, James W.; Sutherland, Earl W.

doi:10.1073/pnas.70.6.1721

Cited by 101 publications

(34 citation statements)

References 23 publications

(10 reference statements)

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“…cGMP production is known to increase in human plasma (22) and platelets (10), rat vas deferens (23), and rabbit gallbladder (24) after a-adrenergic stimulation.…”

Section: 2tmentioning

confidence: 99%

Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension.

Amer¹,

Doba²,

Reis³

1975

Proc. Natl. Acad. Sci. U.S.A.

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Changes in cyclic nucleotide metabolism similar to those characteristic of the chronic forms of hypertension were observed in an acute neurogenic form of hypertension in rats produced by electrolytic lesions of the nucleus tractus solitarii. These changes that were evident 2 hr after the lesions were made included decreased cyclic AMP levels in the heart, increased cGMP: cAMP ratio, cAMP phosphodiesterase (3': 5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) and guanylyl cyclase [GTP pyrophosphate-lyase These studies provide biochemical support to the concept that the sympathetic nervous system may play a critical role in the initiation of the hypertensive syndrome and that chronic hypertension could result from the fixation of the biochemical effects of increased sympathetic activity.There is some evidence that the sympathetic nervous system has a critical role in initiating or sustaining essential hypertension in man (1, 2). How augmented sympathetic nerve activity can produce a fixed arterial hypertension is not known. One view (3, 4) suggests that sustained states of increased sympathetic nerve activity, perhaps caused by heightened states of emotion, can lead to structural vascular changes, which, by reducing the wall-lumen ratio, could result in increased vascular resistance and serve to "fix" the hypertension. Thus, resumption of sympathetic discharge to normal levels would not reverse the increased vascular resistance and the elevated arterial pressure. Transformation of a transient to a fixed state of vascular resistance might thereby serve as a link between neurogenic and essential forms of hypertension. In accord with this view, prolonged arterial hypertension has been elicited in several animal species by emotional or physical stress (5-7), by conditioning (8), or by repetitive electrical stimulation of the brain (9).The mechanisms through which the activity of sympathetic impulses mediates changes in the arterial walls are not understood. One mechanism could be changes in the metabolism of cyclic nucleotides in the blood vessel wall. The cyclic nucleotide system might, therefore, represent the interface MATERIALS AND METHODSMale Sprague-Dawley rats (Carworth Farms, New York) weighing 300-400 g were used in this study. The production of arterial hypertension by bilateral lesions of NTS has been described in detail elsewhere (15). In brief, the rats were anesthetized with halothane (3% in 100% 02 blown over the nose through a face mask). An arterial cannula was inserted in either the femoral or ventral tail artery and the region of the obex was exposed by an occopital carniotomy. A Teflon-coated electrode, with an exposed tip of 0.3 mm and carried by a micromanipulator, was placed into the NTS at the level of the obex. Electrolytic lesions were made by passing a dc current, the wounds were closed, and the animals were permitted to recover from anesthesia. Sham-operated controls were treated similarly but without placing the electrodes in the brain. In some animals, the blood pressure was monit...

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“…cGMP production is known to increase in human plasma (22) and platelets (10), rat vas deferens (23), and rabbit gallbladder (24) after a-adrenergic stimulation.…”

Section: 2tmentioning

confidence: 99%

Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension.

Amer¹,

Doba²,

Reis³

1975

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, by virtue of their ability to produce constriction in vitro as well as their actual or presumed concentrations in cord blood at birth, bradykinin, serotonin, histamine, acetylcholine, prostaglandins A2 and F2 have been suggested as probable chemical mediators of umbilical artery closure (4)(5)(6)(7)(8)(9)(10). Several of these agents have been reported to cause accumulation of cyclic guanosine 3',5'-monophosphate (cGMP)1 in other tissues (11)(12)(13)(14)(15)(16). We have found, as reported below, that bradykinin, histamine, serotonin, and acetylcholine, as well as potassium chloride, in concentrations that cause contraction (4,6), can increase the cGMP content of the arteries without altering the cAMP content.…”

Section: Introductionmentioning

confidence: 99%

Guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate content of human umbilical artery.

Clyman¹,

Sandler²,

Manganiello³

et al. 1975

J. Clin. Invest.

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“…Such muscarinic receptor-linked changes in the cyclic GMP levels have been demonstrated in the heart (George et al, 1970;Watanabe and Besch, 1975;Gardner and Allen, 1976), smooth muscles (Schultz et al, 1973), secretory systems (Smith and Ignarro, 1975;Haymovits and Scheele, 1976), cultured neurons (Matsuzawa and Nirenberg, 1975), and brain slices (Ferrendelli et al, 1970;Hanley and Iversen, 1978). Our results are similar to such findings with respect to the transient accumulation of cyclic GMP in the SA node after an application of acetylcholine.…”

Section: Discussionmentioning

confidence: 99%

Effect of acetylcholine on the norepinephrine-induced positive chronotropy and increase in cyclic nucleotides of isolated rabbit sinoatrial node.

Taniguchi¹,

Fujiwara²,

Lee³

et al. 1979

Circulation Research

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SUMMARY Transmural stimulation of, or application of nicotine to, the isolated rabbit sinoatrial (SA) node resulted in initial negative and late positive chronotropy. Simultaneous application of acetylcholine and norepinephrine produced a similar biphasic chronotropic effect. These procedures produced an initial increase in cyclic guanosine 3':5'-monophosphate (cyclic GMP) and a delayed elevation in cyclic adenosine 3':5'-monophosphate (cyclic AMP). The initial and late effects on rate and nucleotide levels were inhibited by pretreatment with atropine and propranolol, respectively. Pretreatment with atropine shortened the time of maximum increase in cyclic AMP level and heart rate from 3 to 1 minute after the simultaneous application of acetylcholine and norepinephrine and enhanced the positive chronotropic effect. Physostigmine prolonged the duration of the increase in cyclic GMP and negative chronotropic effect after the simultaneous application. These results suggest that when acetylcholine and norepinephrine are present simultaneously in the SA node region, the former interacts predominantly with muscarinic receptors and stimulates the cyclic GMP system, which in effect delays the cyclic AMP elevation and reduces the positive chronotropic effect of norepinephrine. However, these effects of acetylcholine cannot be explained solely on the basis of changes in the cyclic GMP level, because sodium nitroprusside produced a marked elevation of the cyclic GMP levels without decreasing the heart rate and did not affect the norepinephrine-induced increase in pacemaker rate and cyclic AMP. Sodium nitroprusside may affect cyclic GMP pools other than those susceptible to acetylcholine. These cyclic GMP pools may not exert chronotropic effects. Ore Res 45: 493-504, 1979 THE sinoatrial (SA) node of the mammalian heart receives its nerve supply from both the parasympathetic (James and Spence, 1966) and sympathetic (Shindler et al., 1968;Taniguchi et al., 1977) divisions of the autonomic nervous system and, although these two nerves reciprocally regulate the heart rate, the parasympathetic nerve predominates (Voile and Koelle, 1975). Carrier and Bishop (1972) found that when both acetylcholine and norepinephrine were present, the former had a greater effect on heart rate.Previously Taniguchi et al., 1977) that cyclic adenosine 3':5'-monophosphate (cyclic AMP) in the SA node was involved in the positive chronotropic effect of norepinephrine. However, George and associates (1970) snowed that perfusion of the rat heart with acetylcholine resulted in an elevation of cyclic guanosine 3':5'-monophosphate (cyclic GMP) level which paralleled the negative inotropic and chronotropic effects. Watanabe and Besch (1975) suggested that, in the isolated guinea pig ventricle, cyclic GMP mediates the antiadrenergic effects of acetylcholine by specifically antagonizing the inotropic actions of cyclic AMP.Recently, Diamond et al. (1977) showed that sodium nitroprusside markedly increased cat atrial cyclic GMP levels but did not decrease ...

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A New Enzymatic Assay for Guanosine 3′:5′-Cyclic Monophosphate and Its Application to the Ductus Deferens of the Rat

Cited by 101 publications

References 23 publications

Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension.

Changes in cyclic nucleotide metabolism in aorta and heart of neurogenically hypertensive rats: possible trigger mechanism of hypertension.

Guanosine 3',5'-monophosphate and adenosine 3',5'-monophosphate content of human umbilical artery.

Effect of acetylcholine on the norepinephrine-induced positive chronotropy and increase in cyclic nucleotides of isolated rabbit sinoatrial node.

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