pituitrin and methylatropine

The reactions of the vagal cardioaccelerator (VCA) system to changes in mean arterial pressure (MAP) were studied in five beta-adrenoceptor blocked conscious dogs. An increase in MAP was obtained by administration of vasopressin or methoxamine, a decrease by doxazosin or nitroprusside. In the first series of experiments the MAP changes were induced after muscarinic receptor blockade, in a second series both before and after muscarinic blockade. Prior to these experiments, the maximum VCA activity, defined as the difference between maximum heart rate after muscarinic blockade and the rate after additional nicotinic blockade, was determined. We hypothesized that this quantity, as a measure of VCA activity, depends on the prevailing vagal tone. In the first series of experiments, a rise in MAP evoked an increase in heart rate, a fall in MAP indicated decrease. In the second series, when prior to muscarinic blockade the vagal tone was reflexly raised, the subsequent VCA reflex response to the rise in MAP was attenuated. Prior to the muscarinic blockade the vagal tone was reflexly lowered, the VCA reflex response was enhanced. Direct chronotropic effects of MAP-varying drugs were ruled out by the absence of a heart-rate response in experiments on vagotomized animals. We concluded that the vagal cardioaccelerator system is involved in the reflex control of heart rate. Both the VCA reflex response to changes in systemic blood pressure and the maximum VCA activity however, are determined by the prevailing vagal tone.

Topics: Adrenergic beta-Antagonists; Animals; Atropine Derivatives; Autonomic Nervous System; Baroreflex; Blood Pressure; Dogs; Doxazosin; Heart; Heart Rate; Methoxamine; Nitroprusside; Parasympatholytics; Timolol; Vagotomy; Vagus Nerve; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

Saline solutions (NaCl, 2 ml, pH 7.4, 10-598 mosmol/kgH2O) were infused over 4 min in conscious rats, via tail artery catheter or intragastric tube. Intragastric infusions of hyper- and hypotonic solutions caused, within 14.4 +/- 2.2 min, a maximal increase and decrease, respectively, of plasma vasopressin (AVP) relative to time controls (r = 0.97; P less than 0.00001) without affecting systemic plasma osmolality (r = -0.09; P less than 0.92). Mean changes of plasma AVP between 11 and 21 min were also correlated with the osmolality of gastric infusion (r = 0.72; P less than 0.000001), whereas systemic osmolality was unchanged (r = 0.14; P less than 0.42). Systemic infusions caused within 9.0 +/- 2.0 min a maximal change in both plasma AVP (r = 0.82; P less than 0.00001) and systemic osmolality (r = 0.97; P less than 0.00001). However, mean changes of plasma AVP between 11 and 21 min weakly correlated with the osmolality of systemic infusions (r = 0.27; P less than 0.20), although correlations between mean changes of systemic osmolality and the osmolality of systemic infusions were significant (r = 0.72; P less than 0.00001). Lack of correlations with mean arterial pressure and heart rate suggest that hemodynamic changes did not mediate the AVP responses. Pretreatment with atropine methyl bromate (2 mg/kg) abolished the AVP response to gastric but not systemic infusions of hypertonic saline. These results indicate that a splanchnic cholinergic receptor mechanism modulates AVP secretion during a moderate gastric intake of salt or water.

Topics: Animals; Atropine Derivatives; Blood Pressure; Heart Rate; Hypotonic Solutions; Kinetics; Male; Rats; Rats, Inbred Strains; Receptors, Angiotensin; Receptors, Vasopressin; Saline Solution, Hypertonic; Sodium Chloride; Splanchnic Circulation; Vasopressins; Water-Electrolyte Balance

The cardiovascular effects of centrally administered cholinomimetics were examined in conscious Long-Evans and Brattleboro rats. Carbachol (1 microgram/kg) or physostigmine (50 micrograms/kg) induced a long-lasting increase in blood pressure and a decrease in heart rate in Long-Evans rats whereas no bradycardia was observed in Brattleboro rats, and the pressor response was significantly less than that in Long-Evans rats. The cardiovascular responses to nicotine (30 micrograms/kg) in Brattleboro rats were not different from those in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5Tyr(Me) arginine vasopressin, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in Long-Evans rats. However, the pressor response to carbachol in Brattleboro rats was still significantly less than that in Long-Evans rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in Long-Evans rats and completely eliminated it in Brattleboro rats. Combined intravenous treatment with phentolamine and vasopressin antagonist completely eliminated the pressor response to carbachol in Long-Evans rats. Centrally administered methylatropine eliminated either the hypertensive or bradycardic response to carbachol in Long-Evans rats. These results indicate that the pressor and bradycardic response to carbachol or physostigmine is mediated by the central muscarinic receptor mechanism. Hypertensive response to intracerebroventricularly administered carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by vasopressin.

Topics: Animals; Arginine Vasopressin; Atropine Derivatives; Autonomic Nervous System; Blood Pressure; Bradycardia; Carbachol; Cardiovascular Physiological Phenomena; Cardiovascular System; Deamino Arginine Vasopressin; Hypertension; Injections, Intraventricular; Male; Nicotine; Parasympatholytics; Phentolamine; Physostigmine; Rats; Rats, Brattleboro; Vasopressins

The influence of the slow channel calcium entry blocker, nifedipine, and the slow channel calcium entry promoter, BAY-K 8644, on receptor-mediated hemodynamic responses was studied in chronically instrumented, conscious dogs. Following ganglionic, cholinergic, and beta-adrenergic blockade, equipressor doses of phenylephrine (0.6 microgram/kg iv), a selective alpha 1-adrenoceptor agonist, and B-HT 933 (20 micrograms/kg iv), a selective alpha 2-adrenoceptor agonist, as well as a nonadrenergic vasoconstrictor, vasopressin (0.003 IU/kg) were administered before and after infusions of nifedipine or BAY-K 8644 (0.25, 0.5, 1.0, and 2.0 micrograms X kg-1 X min-1). In doses producing minimal or no haemodynamic effects, nifedipine caused dose-related attenuation from control of phenylephrine- (from 26 +/- 3 to 8 +/- 1 mmHg), B-HT 933- (from 30 +/- 2 to 5 +/- 2 mmHg), and vasopressin- (24 +/- 1 to 2 +/- 2 mmHg) mediated changes in mean arterial pressure. In contrast, BAY-K 8644 produced dose-related potentiation from control of the same pressor responses (phenylephrine, 24 +/- 2 to 41 +/- 3 mmHg; B-HT 933, 28 +/- 3 to 46 +/- 2 mmHg; vasopressin, 25 +/- 3 to 45 +/- 5 mmHg). In addition, BAY-K 8644 produced a marked increase in the duration of the pressor response produced by all three agonists. Thus, in conscious dogs, alpha 1-, alpha 2-, and vasopressin-mediated pressor responses are strongly modulated by transmembrane calcium flux and can be influenced by dihydropyridine slow channel calcium agonists and antagonists.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Atropine Derivatives; Azepines; Calcium; Dogs; Female; Hemodynamics; Hexamethonium; Hexamethonium Compounds; Ion Channels; Male; Nifedipine; Phenylephrine; Propranolol; Receptors, Adrenergic, alpha; Receptors, Angiotensin; Receptors, Vasopressin; Vasopressins

The effects of intracerebroventricular administration of bombesin on mean arterial pressure and heart rate were studied in conscious, freely moving rats. Injection of bombesin produced dose-dependent elevations of mean arterial pressure and reductions of heart rate. These effects were not caused by leakage of bombesin into the peripheral circulation. Adrenalectomy abolished the pressor action of bombesin but did not alter bombesin-induced bradycardia. Systemic phentolamine pretreatment prevented bombesin-induced changes of mean arterial pressure, whereas rats treated intravenously with captopril or a vasopressin antagonist still exhibited pressor responses to bombesin administration. Bombesin-induced bradycardia was partially antagonized by intravenous atropine methyl nitrate administration, whereas systemic injections of propranolol did not modify this response. It is concluded that bombesin acts within the central nervous system to elevate mean arterial pressure through an adrenal-dependent mechanism involving alpha-adrenergic receptors and to reduce heart rate through an adrenal-independent mechanism involving, at least in part, cardiac parasympathetic nervous activation.

Topics: Animals; Arginine Vasopressin; Atropine Derivatives; Blood Pressure; Bombesin; Captopril; Cardiovascular System; Central Nervous System; Consciousness; Dose-Response Relationship, Drug; Heart Rate; Injections, Intraventricular; Male; Peptides; Phentolamine; Propranolol; Rats; Rats, Inbred Strains; Vasopressins