RESUMEN
Atrial natriuretic factor (ANF) has been localized in periventricular brain areas involved in cardiovascular and fluid control. We investigated the effect of intracerebroventricular (icv) ANF (alpha-rat atriopeptin III) on renal sodium excretion in unilaterally nephrectomized, conscious unrestrained rats fitted with a chronic ureteral catheter. Isotonic NaCl (1 ml/h) was infused intravenously. ANF injected at doses (icv) of 1 ng (n = 6), 100 ng (n = 7), and 1 microgram (n = 7) reduced urinary sodium excretion (all values mumol/45 min, means +/- SE) from 111.6 +/- 24.4 to 83 +/- 20 (P less than 0.05), from 96.9 +/- 25.2 to 55 +/- 14 (P less than 0.01), and from 90.8 +/- 14.2 to 51 +/- 9 (P less than 0.01), respectively, whereas urinary flow rate did not change. The antinatriuretic effect was immediate in onset and lasted for greater than or equal to 60 min. Blood pressure remained unaltered. ANF (100 ng icv) increased efferent sympathetic renal nerve activity (+36%; n = 6, P less than 0.05), plasma renin activity (4.6 +/- 0.6 to 7.5 +/- 0.5 pmol angiotensin I.ml-1.h-1; n = 9, P less than 0.01), plasma angiotensin II (68.7 +/- 2.5 to 84.7 +/- 3.4 fmol/ml; n = 8, P less than 0.01), and aldosterone (22.3 +/- 3.6 to 37.2 +/- 4.0 ng/ml; n = 9, P less than 0.02). Renal denervation reduced the antinatriuretic effect of ANF by 37%. We conclude that brain ANF has antinatriuretic actions, which may be partly explained by activation of renal nerves.
Asunto(s)
Factor Natriurético Atrial/farmacología , Encéfalo/fisiología , Riñón/metabolismo , Cloruro de Sodio/metabolismo , Aldosterona/sangre , Angiotensina II/sangre , Animales , Inyecciones Intraventriculares , Riñón/inervación , Masculino , Fenómenos Fisiológicos del Sistema Nervioso , Concentración Osmolar , Ratas , Ratas Endogámicas , Renina/sangreRESUMEN
Arginine vasopressin (AVP) injected intracerebroventricularly (i.c.v.) in the nanogram range elicits increases in mean arterial blood pressure (MAP), heart rate (HR) and efferent sympathetic nerve activity (SpNA) via central V1 AVP receptor stimulation. In this study in conscious rats we investigated, whether the cardiovascular and sympathetic responses can be augmented by repeated central applications of AVP, as has been previously shown for the convulsive responses to higher i.c.v. doses of the peptide. The AVP-induced pressor (0.1 and 1.0 ng) and the SpNA (0.1 ng) responses were significantly enhanced by a second AVP challenge 24 h after the first injection. With higher doses of the peptide (3 ng), the blood pressure responses were not different between two subsequent injections, but barrel rotation occurred in 21% of the animals upon the second challenge. The pressor responses to a threshold i.c.v. dose of 1 ng angiotensin II (ANG II) were not enhanced upon a second ANG II challenge. Our results demonstrate that AVP, unlike ANG II, can sensitize central mechanisms leading to increased MAP and SpNA responses.
Asunto(s)
Fibras Adrenérgicas/efectos de los fármacos , Arginina Vasopresina/farmacología , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Fibras Adrenérgicas/fisiología , Animales , Relación Dosis-Respuesta a Droga , Inyecciones Intraventriculares , Masculino , Ratas , Ratas EndogámicasRESUMEN
Atrial natriuretic factor (ANF) and angiotensin II (ANG II) have been demonstrated in close vicinity in forebrain areas involved in the central fluid and electrolyte regulation. Previous reports suggested an inhibitory effect of ANF on some of the central actions of ANG II, such as water intake and vasopressin release. In the present study in conscious, unrestrained, sodium-repleted rats we investigated the effects of intracerebroventricularly (i.c.v.) administered ANF (alpha r-APIII) on the central natriuretic action of ANG II. Urine was collected through a novel chronically implanted ureteral catheter. I.c.v. injections of ANG II (100 pg) produced a marked natriuresis of rapid onset without altering urinary volume or blood pressure. Pretreatment with ANF (100 pg, 1 ng, 100 ng i.c.v.) 5 min before ANG II dose-dependently antagonized the ANG II-induced natriuretic effect. The lowest dose caused approximately 50% reduction, the intermediate dose a complete abolition and the highest dose even a reversal of the ANG II-induced natriuretic effect to salt retention. Urinary volume and blood pressure were not altered by the combined treatment with ANG II and ANF. Our results support the idea of a functional antagonism between ANG II and ANF in the central fluid and electrolyte control.
Asunto(s)
Angiotensina II/farmacología , Factor Natriurético Atrial/administración & dosificación , Natriuresis/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Ratas , Ratas EndogámicasRESUMEN
To elucidate mechanisms of angiotensin II (Ang II)-related hypertension, we infused angiotensin (76 ng/min s.c.) into rats with minipumps for 10-14 days. Control rats received sham pumps. We measured blood pressure by tail-cuff, and the excretion of aldosterone and prostaglandins (PG) (PGE2, prostacyclin derivative 6kPGF1 alpha, and thromboxane [Tx] derivative TxB2). Angiotensin II increased blood pressure by 20 mm Hg by day 2 and by 90 mm Hg by day 10. Aldosterone excretion increased from 10 to 70 ng/day in Ang II rats by day 7. Urine PGE2 did not increase in angiotensin rats; however, both 6kPGF1 alpha and TxB2 excretion increased with angiotensin. Control rats had no changes in any of these parameters. A sympathetic component was tested in a separate group of angiotensin rats that received phenoxybenzamine (300 micrograms/kg/day) during angiotensin infusion; their increase in blood pressure of 40 mm Hg at 10 days was less than in those rats with angiotensin alone but more than in control rats. Phenoxybenzamine did not influence the angiotensin-induced increases in excretion of 6kPGF1 alpha or TxB2. Additional groups of conscious angiotensin and control rats were equipped with splanchnic nerve electrodes on day 14 for recording of sympathetic nerve activity. Angiotensin rats had greater basal sympathetic nerve activity than the control rats. Incremental methoxamine injections demonstrated altered baroreceptor reflex function in rats receiving angiotensin. We conclude that increased blood pressure with chronic angiotensin infusion is accompanied by increased production of aldosterone and increased sympathetic tone. The latter may be modulated by PG.
Asunto(s)
Angiotensina II/farmacología , Hipertensión/inducido químicamente , Sistema Nervioso Simpático/fisiopatología , 6-Cetoprostaglandina F1 alfa/metabolismo , Aldosterona/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Dinoprostona/metabolismo , Hipertensión/fisiopatología , Masculino , Metoxamina/farmacología , Fenoxibenzamina/farmacología , Presorreceptores/fisiología , Ratas , Ratas Endogámicas , Receptores Adrenérgicos alfa/efectos de los fármacos , Análisis de Regresión , Nervios Esplácnicos/fisiopatología , Tromboxano B2/metabolismoRESUMEN
The effects of intracerebroventricular (i.c.v.) injections of angiotensin II (ANG II, 10 pg, 100 pg and 10 ng) on renal sodium excretion were investigated in conscious rats instrumented with a chronic urethral catheter. ANG II increased renal sodium excretion dose-dependently with a threshold i.c.v. dose of 10 pg. Only after the highest dose was a concomitant increase in arterial blood pressure and urinary flow observed. The ANG II-induced natriuresis began within 5 min of the i.c.v. injection and lasted for more than 1 h. The angiotensin receptor antagonist saralasin (1 ng, i.c.v.) largely prevented the natriuretic effect of i.c.v. injected ANG II (100 pg). Our results lend further support to the hypothesis that brain ANG II by its potent natriuretic actions may be instrumental in central osmotic control.
Asunto(s)
Angiotensina II/farmacología , Encéfalo/fisiología , Sodio/orina , Animales , Encéfalo/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Inyecciones Intraventriculares , Masculino , Ratas , Ratas EndogámicasRESUMEN
In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Sistema Cardiovascular/efectos de los fármacos , Mecanismos de Defensa , Sustancia P/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Antagonistas Adrenérgicos beta/farmacología , Animales , Atropina/farmacología , Hemodinámica/efectos de los fármacos , Miembro Posterior/irrigación sanguínea , Inyecciones Intraventriculares , Masculino , Hormonas Hipofisarias/metabolismo , Ratas , Ratas Endogámicas , Vasopresinas/antagonistas & inhibidoresRESUMEN
Arginine vasopressin (AVP) containing neurones and pathways have been localized in various cardiovascular control centers of the central nervous system in rats. AVP influences cardiovascular regulation when injected into various areas of the central nervous system. The blood pressure increases in response to central AVP injections were shown to be initiated by stimulation of central V1-AVP receptors and mediated by stimulation of sympathetic outflow to the periphery. On the other hand, AVP has also been shown to attenuate the pressor responses to electrical stimulation of the mesencephalic reticular formation when injected into the brain ventricular system. In addition, AVP can participate in cardiovascular regulation by modulating baroreceptor reflex sensitivity. We have shown that in rats peripheral (hormonal) AVP can sensitize the heart rate component of the baroreceptor reflex by acting on V2-AVP receptors accessible from the blood, while at the same time central (neuronal) AVP can attenuate the baroreceptor reflex through brain V1-AVP receptors that cannot be reached from the blood. Binding and functional studies favour the existence of V1-AVP receptors in the central nervous system, whereas evidence for central V2-AVP receptors is still scarce. The role of AVP in hypertension remains controversial, but recent evidence suggests that a discordance between the various central and peripheral cardiovascular actions of AVP, rather than its hormonal vasopressor effects, may contribute to the pathogenesis of hypertension.
Asunto(s)
Arginina Vasopresina/farmacología , Fenómenos Fisiológicos Cardiovasculares , Hipertensión/fisiopatología , Animales , Sistema Cardiovascular/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Presorreceptores/efectos de los fármacos , Presorreceptores/fisiología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas , Ratas Endogámicas WKY , Reflejo/efectos de los fármacosRESUMEN
We tested the baroreflex in conscious, stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto controls (WKY) with incremental bolus injections of nitroprusside and methoxamine. The change in heart rate (HR) per change in mean blood pressure (MAP) was greater in WKY than in SHRSP. In contrast, the change in splanchnic nerve activity (SpNA) per change in MAP was greater in SHRSP than in WKY. The sympathetic outflow in SHRSP seems more reactive to blood pressure changes than in WKY. The discordance in HR and SpNA changes suggests that the integration of autonomic function in SHRSP is impaired.
Asunto(s)
Frecuencia Cardíaca , Hipertensión/fisiopatología , Presorreceptores/metabolismo , Nervios Esplácnicos/metabolismo , Animales , Presión Sanguínea , Hipertensión/tratamiento farmacológico , Masculino , Metoxamina/farmacología , Nitroprusiato/farmacología , Ratas , Ratas Endogámicas WKYRESUMEN
To elucidate the relationship between responses in sympathetic outflow to incremental changes in blood pressure, we performed baroreflex activation experiments in conscious, stroke-prone, spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto (WKY) rats. We gave incremental bolus injections of nitroprusside and methoxamine and measured mean blood pressure (MAP), heart rate, and splanchnic nerve activity (SpNA). Change in heart rate per change in blood pressure was greater in WKY rats than in SHRSP indicating the decrease in baroreceptor sensitivity displayed in the latter strain. In contrast, change in SpNA per change in blood pressure was greater in SHRSP than in WKY rats. These findings suggest that sympathetic outflow in SHRSP is more reactive to blood pressure changes than in WKY rats. The discordance in heart rate and SpNA changes supports the notion that central neural integration of autonomic function in SHRSP is impaired.
Asunto(s)
Presión Sanguínea , Trastornos Cerebrovasculares/fisiopatología , Hipertensión/fisiopatología , Presorreceptores/fisiopatología , Reflejo , Nervios Esplácnicos/fisiopatología , Animales , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Metoxamina/farmacología , Nitroprusiato/farmacología , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Reflejo/efectos de los fármacos , Nervios Esplácnicos/efectos de los fármacosRESUMEN
Plasma vasopressin sensitizes the baroreceptor reflex, whereas vasopressin given into the cerebral ventricle overrides the baroreceptor reflex by means of sympathetic stimulation. To test the hypothesis that arginine vasopressin stimulates two different receptor subtypes (V1 and V2) in the central nervous system, we measured the baroreceptor reflex (change in pulse interval vs change in blood pressure) after administering methoxamine (10-300 micrograms/kg i.v.) in conscious rats. Animals were pretreated either with a V1 vasopressin receptor antagonist administered intravenously or intracerebroventricularly, or with a V2 receptor antagonist administered intravenously. The central V1 antagonist caused sensitization of the baroreceptor reflex, whereas the intravenous V2 antagonist attenuated it. The intravenous V1 vasopressin antagonist had no effect on baroreceptor reflex sensitivity. When the experiments were repeated in rats with hereditary diabetes insipidus, neither antagonist influenced the baroreceptor reflex. Volume expansion lowered circulating vasopressin levels and also attenuated the baroreceptor reflex--effects similar to those observed with the intravenous V2 antagonist. We conclude that vasopressin sensitizes the baroreceptor reflex through V2 receptors accessible from the blood and inhibits the reflex through V1 receptors in the brain that cannot be reached from the blood. These observations suggest a direct interaction between hormonal and neuronal vasopressin in cardiovascular control.
Asunto(s)
Arginina Vasopresina/fisiología , Encéfalo/fisiología , Presorreceptores/fisiología , Reflejo , Animales , Arginina Vasopresina/sangre , Arginina Vasopresina/farmacología , Presión Sanguínea/efectos de los fármacos , Encéfalo/efectos de los fármacos , Masculino , Presorreceptores/efectos de los fármacos , Pulso Arterial/efectos de los fármacos , Ratas , Ratas Endogámicas , Receptores de Angiotensina/análisis , Receptores de Angiotensina/efectos de los fármacos , Receptores de Angiotensina/fisiología , Receptores de Vasopresinas , Reflejo/efectos de los fármacosRESUMEN
The central cardiovascular actions of arginine vasopressin (AVP) and the role of this peptide in the modulation of baroreceptor reflex (BRR) sensitivity were investigated in conscious, chronically instrumented rats. Intracerebroventricular (i.c.v.) injections of AVP (1-100 ng) produced dose-dependent pressor effects together with increases in heart rate, splanchnic, and renal sympathetic nerve activity and a reduction of mesenteric blood flow. These responses were prevented by i.c.v. pretreatment with a V1-AVP receptor antagonist. Furthermore, the central pressor effects of AVP were abolished by peripheral alpha-adrenoceptor blockade with phentolamine. In contrast to the i.c.v. injections, intravenous (i.v.) or intracarotid injections of AVP produced pressor responses accompanied by bradycardia and a decrease in sympathetic nerve activity. Intracerebroventricular pretreatment with a V1-AVP receptor antagonist shifted the slope of the BRR curve (increases in pulse interval plotted against increases in systolic blood pressure in response to i.v. methoxamine) toward higher sensitivity, whereas i.v. pretreatment with a V2-AVP receptor antagonist shifted the slope of the BRR curve toward lower sensitivity of the reflex. These findings suggest that central (neuronal) AVP, by acting on V1-AVP receptors in the brain, participates in central pressor mechanisms, activates the sympathetic nervous system, and desensitizes the BRR. Conversely, circulating (hormonal) AVP can sensitize the BRR by acting on V2-AVP receptors accessible from the blood. Our data provide evidence pointing to a direct interaction between the neuronal and the hormonal axis of the AVP system within cardiovascular control.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Neuronas/fisiología , Presorreceptores/efectos de los fármacos , Vasopresinas/farmacología , Animales , Arginina Vasopresina/farmacología , Hemodinámica/efectos de los fármacos , Inyecciones Intraventriculares , Masculino , Ratas , Ratas Endogámicas , Receptores de Angiotensina/efectos de los fármacos , Receptores de Vasopresinas , Reflejo/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacosRESUMEN
The centrally induced effects of angiotensin II and substance P on the cardiovascular system and on neuronal efferent activity of the splanchnic, renal, and adrenal nerves were investigated in chronically instrumented conscious rats. The pressor responses to substance P injected into the lateral brain ventricle were accompanied by marked and short latency increases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a rise in plasma noradrenaline and adrenaline. Behaviorally, an arousal-type reaction was observed. In contrast, the pressor responses to intracerebroventricular angiotensin II were associated with initial decreases in heart rate, cardiac output, splanchnic, renal, and adrenal nerve activity, and a fall in plasma noradrenaline at the time of the maximal blood pressure increase. In some but not all animals, a second blood pressure peak associated with increases in heart rate and splanchnic nerve activity was observed after several minutes. Incomplete chronic sinoaortic baroreceptor deafferentiation prevented the angiotensin II-induced fall in heart rate but not the initial fall in splanchnic nerve activity. The decreases in splanchnic nerve activity also occurred in diabetes insipidus rats and persisted in Long Evans rats after vascular vasopressin receptor blockade with d(CH2)5AVP, despite marked reductions of the pressor responses in both groups. Peripheral alpha-adrenoceptor blockade with prazosin or ganglion blockade with hexamethonium inhibited the central angiotensin II pressor responses only in combination with vasopressin receptor blockade. On the other hand, either sympatholytic drug, alone, abolished the pressor responses in the diabetes insipidus rats. This indicates that in intact conscious rats the central pressor effects of angiotensin II are initiated by vasopressin release but become dependent on the sympathetic nervous system when vasopressin is absent or not effective. When rats were allowed to drink in response to angiotensin II, a further sharp rise in blood pressure occurred, together with increases in heart rate and splanchnic nerve activity. The results demonstrate fundamental differences in the mechanisms by which central pressor peptides can influence cardiovascular and autonomic function. It is conceivable that the distinct sympathetic response patterns to central angiotensin II and substance P receptor stimulation form part of a specific cardiovascular adjustment to the individual behavioral reactions, such as drinking, as in the case of angiotensin II, or arousal within the central processing of pain, as in the case of substance P.