Participation of nitric oxide in the nicotine-induced relaxation of the cat lower esophageal sphincter.

The participation of nitric oxide in the relaxation of the cat lower esophageal sphincter muscle strip in response to electrical field stimulation or administration of nicotine was studied. The nicotine-induced relaxation was mediated via a neuronal pathway, since it was inhibited by administration of hexamethonium or tetrodotoxin. Inhibition of nitric oxide biosynthesis by N-nitro-L-arginine decreased the relaxation induced by nicotine (50 microM) or field stimulation. With the maximal concentration of N-nitro-L-arginine (1 mM) electrical field stimulation-induced relaxation was abolished, while nicotine-induced relaxation decreased by 70%. L-Arginine (1 mM) partly restored this relaxation. Desensitization of P2x receptors by alpha, beta methylene-adenosine 5-triphosphate (alpha, beta-m-ATP) did not change the relaxation induced by either electrical field stimulation or administration of nicotine. It is therefore suggested that the field stimulation-induced relaxation is mediated by the release of nitric oxide, but in the nicotine-produced relaxation is only partly due to nitric oxide, other factor(s) might be also be involved.

Role of nitric oxide in mediating non-adrenergic non-cholinergic relaxation of the cat ileocecal sphincter.

The participation of nitric oxide (NO) in field stimulation- or nicotine-evoked non-adrenergic non-cholinergic (NANC) relaxation of cat ileocecal sphincter was studied in vitro. During a 30 microM noradrenaline-induced contraction, both the application of electrical field stimulation (2-20 Hz, 0.2 ms, supramaximal current intensity, 10 s duration) and (-)-nicotine (10-500 microM) produced a tetrodotoxin-sensitive relaxation. The maximal relaxation was observed at 10 Hz or 100 microM (-)-nicotine. In 12 out of 19 strips the pretreatment with N omega-nitro-L-arginine (100 microM) decreased the amplitude of the field stimulation-evoked relaxation, while in the remaining strips the relaxation was transformed into a contraction. By increasing the concentration of N omega-nitro-L-arginine up to 1 mM all strips responded to field stimulation with a frequency-dependent tetrodotoxin-resistant contraction. N omega-Nitro-L-arginine (100 microM) completely inhibited the nicotine-induced relaxation. L-Arginine (1 mM) restored the amplitude of both field stimulation- and nicotine-evoked relaxations. These data indicate that NO appears to be involved in both field stimulation- and nicotine-evoked NANC relaxations. Evidence has been obtained for the existence of tetrodotoxin-resistant NANC contraction in cat ileocecal sphincter.

Antiexudative and capillaritonic effects of procyanidines isolated from grape seeds (V. Vinifera).

A purified and enriched fraction, containing procyanidines, was isolated from grape seeds of Bulgarian sorts of Vitis Vinifera. The effects of procyanidines on the local oedema, produced by subplantar injection of carrageenin and dextran in the hind rat paw, were studied. We also tested their effect on the capillary permeability using intravenous injection of Evans blue and local irritation by xylene. Procyanidines at a dose of 2 mg/kg applied orally three times daily for 6 days inhibited the carrageenin-induced hind paw oedema. On the same schedule of administration these compounds inhibited the dextran-induced oedema 4 hours after the development of the process. Procyanidines stabilized the capillary wall and prevented the increase of capillary permeability caused by local cutaneous application of xylene.

A new analogue of substance P with antagonistic properties in renal and pulmonary arteries.

The effects of a new analogue of substance P (SP-A) and its interaction with substance P (SP) were studied in vitro isolated preparations from rabbit renal arteries and rat renal and pulmonary arteries. SP-A in did not affect the resting tone and the contractions of the rabbit renal arteries, evoked by field electrical stimulation (FES) but dose-dependently (10(-10)M - 5 X 10(-8)M) antagonized the inhibitory effects of SP on the FES-provoked contractions, the antagonism being of a non-competitive type. In the rat renal arteries SP had two different effects--depression of the FES-evoked contractions, and increase of the resting tone. SP-A did not exert per se effects on the tone and on the electrically-provoked contractions in these arteries. SP-A non-competitively antagonized both actions of SP in the same vessels. In rat pulmonary arteries SP increased the resting tone, whereas SP-A did not affect the resting tone and the FES-induced contractions. SP-A non-competitively antagonized the tone-increasing action of SP. The new analogue of SP may be useful in studying the mechanism of action of SP and its role in physiological and pathological reactions.

Effects of substance P on isolated preparations from rabbit and rat renal arteries.

Substance P (SP) increased the tone of isolated ring preparations from renal and pulmonary arteries from rat but not from rabbit. Indomethacin decreased the amplitude of SP-evoked tone by 50%. SP inhibited in a dose-dependent manner the electrically-evoked contractions of the rabbit and rat renal arteries. The threshold concentrations producing inhibitory effects of SP were 10(-12) M for rabbit arteries and 10(-9) M for rat arteries. The maximal inhibition was observed at 10(-8) M and 10(-6) M, respectively. In the renal arteries of spontaneously hypertensive rats SP potentiated the electrically-evoked contractions. SP caused relaxation of the rabbit renal arteries, previously contracted with noradrenaline (10(-7) M), high [K+]0 (30 mM) and prostaglandin F2 alpha (10(-6) M). The results have shown that the effects of SP on the arterial contractions depend on the species and on the normal or pathologic conditions. A direct action of SP on the arterial muscle cells is suggested.

Ionic interactions in the smooth muscles of cat pulmonary artery and portal vein.

The contractile activity of isolated smooth-muscle preparations of pulmonary artery and portal vein was recorded under isometric conditions and the changes in the membrane potential were recorded by the sucrose gap method. The replacement of Na+ by sucrose or cholinechloride ([Na+]o = 0) in the presence of phentolamine and atropine causes contraction of the smooth-muscle strips, characterized by initial fast and subsequent slow tonic component. The contraction is accompanied by hyperpolarization of the membrane. D600 (10(-5) M) and sodium nitroprusside (10(-5) M) do not influence the tonic component of the [Na+]o = 0-induced contraction. Low Na-content in the solution ([Na+]o = 15.5 mM) causes brief contraction only of the portal vein strips. In Ca-free solution the tone of the arterial preparations does not change, while the tone of portal vein strips decreases and phasic contractions are inhibited. In Ca-free solution or after pretreatment of the strips with 10 mM LaCl3, substitution of sodium induces a slowly developing contraction without initial fast component. Pretreatment of the preparations with ouabain (10(-4) M) or their preincubation in K-free solution potentiates the [Na+]o = 0-induced contraction. The results obtained exclude membrane-potential-dependent processes in the development of the [Na+] o = 0-induced contraction and support the existence of Na+-Ca2+ exchange mechanism in the smooth muscles of cat pulmonary artery and portal vein.

Vascular effects of the carotid baroreceptor reflex upon increased tissue osmolarity.

Acute experiments were carried out on the vascular bed of cat hind leg upon perfusion at constant blood flow and increased tissue osmolarity through intraarterial hypertonic infusion. The activity of the carotid baroreceptors was changed by means of bilateral carotid fusion. The activity of the carotid baroreceptors was changed by means of bilateral carotid occlusion and by increasing or decreasing the carotid blood flow. Hyperosmolarity reduced both the increase in the vascular contraction in response to the decreased baroreceptor activity and the decrease of the contraction resulting from the increased baroreceptor activation. The smaller rise in the contraction was connected with the direct hyperosmolarity inhibition of vascular contractility. The smaller decrease in the vascular response was connected with the smaller initial contraction of the vascular muscle due to hyperosmolarity inhibition of the spontaneous contractile activity. The results presented show that upon increasing tissue osmolarity the resistance vessels manifest the same behaviour with respect to the changes in the activity of the carotid baroreceptors as in the case of muscle exercises. This supports the assumption of the possible participation of the decrease in the neurogenic vascular tone in the appearance of hyperosmolarity vasodilation and of exercise hyperemia.

Peripheral determination of the vascular effect of the carotid depressor reflex.

Experiments were carried out to study the changes in the vascular muscle contraction and the vascular bed resistance of cat hind leg in response to identical activation of the sinocarotid baroreceptors, however with different initial functional state of the vascular bed. Determining the dilatatory responses of the vascular bed in a state of rest, of increased tissue osmolarity and upon increase in femoral blood flow without the presence of autoregulatory reaction, it was shown that the baroreceptor decrease of the vascular contraction is peripherally conditioned by the value of the initial contraction, while the baroreceptor decrease of the resistance is determined by the ratio between the initial contraction and the initial radius. The peripheral determination of the organ differentiation of the depressor effect of the carotid baroreceptor reflex is discussed on the basis of these results.

Mechanism of hyperosmolarity inhibition of vascular contractility.

Studies were made of the responses of the vascular bed of cat hind leg to intraarterial injection of noradrenaline, angiotensine, tyramine and vasopressine, as well as of carotid occlusion upon increasing the tissue osmolarity through intraarterial hypertonic infusion. The limb was perfused at constant blood flow. Hyperosmolarity inhibited the contractile effects of all stimuli studied. The inhibition of the contractility was greater in the case of tyramine and identical in the case of the remaining vasoconstrictor agents. Increased KCl content or the addition of L-ascorbic acid to the hypertonic solution with preservation of the same hyperosmolarity reduced the inhibition of the contractile responses to noradrenaline and angiotensine. The restoration of the contractility was much more pronounced upon simultaneous increase in the KCl content and addition of L-ascorbic acid. No recovery of the contractile effect of tyramine was observed. The mechanism of hyperosmolarity inhibition of the vascular contraction is discussed. In all vasoconstrictor stimuli the inhibition is connected primarily with disruption of the transmembrane exchange of Na+ and Ka+. In some vasoconstrictor agents, e. g. tyramine, there is disturbance in the specific mechanism connected secondarily with vascular contraction.

Participation of the cardiopulmonary baroreceptors in the buffering of fast changes in the arterial pressure.

Acute experiments on cats are carried out to study the effect on the value of the pressor and depressor responses of the systemic arterial pressure (SAP) of the rise in the central venous pressure (CVP), occurring upon the administration of some hyper- and hypotensive agents. The responses of SAP to intravenous injection of different doses of noradrenaline and acetylcholine are determined at rest, after vagotomy, during intravenous infusion of dextrane solution and after vagotomy during infusion. It is shown that when the hypertensive agent causes a rise in CVP in addition to its pressor effect, the pressor response is subjected both to carotid and to aortic buffering as a result of the increased SAP, as well as to cardiopulmonary buffering due to the rise in CVP. In the case of the hypotensive agent the rise in CVP does not influence the value of the depressor SAP response, since the changes in the activation of the cardiopulmonary and arterial baroreceptors are in different directions. Evidence is presented in support of the assumption that the cardiopulmonary inhibition is transmitted along extravagal afferent ways in addition to being transmitted along the vagal nerves.