Sustained acute voltage-dependent blood pressure decrease with prolonged carotid baroreflex activation in therapy-resistant hypertension.

OBJECTIVE: Chronic carotid baroreflex stimulation (Rheos system) has been shown to effectively reduce blood pressure in patients with resistant hypertension. Upon acute stimulation blood pressure also falls as a function of voltage. the aim of this study is to evaluate whether this voltage-dependent blood pressure decrease is preserved after long-term carotid baroreflex stimulation. METHODS: Forty-five patients implanted with Rheos underwent a voltage response test (VRT) before the start of carotid baroreflex activation (1m), as well as after 4 (4m) and 13 months (13 m) of device implantation. After switching off the device for 10 min (0 V), we started the VRT by increasing voltage from 1 to 6 V, by 1-V steps every 5 min. Blood pressure and heart rate were measured at the end of every step. RESULTS: At 1m, mean blood pressure was 178/101 mmHg at 0 V and fell to 142/83 mmHg at 6 V. Heart rate fell from 75 to 65 beats/min. At 4m and 13 m mean blood pressure was significantly lower compared to 1m when VRT started at 0 V (170/96 and 161/93 mmHg, respectively). However, pattern of blood pressure decrease during VRT was comparable with this at 1m. Maximum SBP reduction during VRT did not change with long-term therapy. CONCLUSIONS: Acute voltage-dependent blood pressure and heart rate decrease with electrical baroreflex stimulation is preserved after at least 1 year of continuous activation in patients with resistant hypertension. This indicates that response adaptation and nerve fatigue are very unlikely in long-term carotid baroreflex activation.

Electrical stimulation of deep peroneal nerve mimicking acupuncture inhibits the pressor response via capsaicin-insensitive afferents in anesthetized rats.

OBJECTIVE: To assess the inhibitory modulation of blood pressure by stimulation of the deep peroneal nerve (DPN) and to determine the involvement of nociceptive fibers in the modulation. METHODS: All the animals were divided into six groups (A-F). The rats in groups A and B received no pretreatment. The rats in groups C and D received subcutaneous injection of capsaicin or control vehicle, respectively, near the DPN for 2 days. Those in groups E and F had the DPN exposed to capsaicin or control vehicle, respectively, for 20 min. Subsequently, pressor responses were induced by stimulation of paraventricular nucleus (PVN) either electrically (groups A and C C-F) or chemically via injection of glutamate (group B). After two stable pressor responses (baseline), all groups were subject to 5-min DPN stimulation followed by PVN stimulation for 10 s. Arterial blood pressure, heart rate, and electrocardiogram were recorded. The pressor response was calculated as the difference in the mean arterial pressure (MAP) before and after PVN stimulation, and changes from baseline in pressor response after DPN stimulation were compared between the groups. RESULTS: Increases of MAP of 22.88±2.18 mm Hg and 20.32±5.25 mm Hg were induced by electrical (group A) or chemical (group B) stimulation of the PVN, respectively. These pressor responses were inhibited by stimulation of the DPN, and the MAP was reduced to 12.00±2.10 mm Hg in group A (n=6, P<0.01) and 7.00±2.85 mm Hg in group B (n=6, P<0.01). Subcutaneous injection of capsaicin (125 mg/kg) near the DPN in group C (n=7) had no effect on the inhibitory effect of DPN stimulation compared with the group D (n=9), and neither did blockade of nociceptive fibers with capsaicin in group E (n=6) compared with group F (n=8). CONCLUSION: Stimulation of the DPN mimicking acupuncture has an inhibitory effect on the pressor response, and the effect is mediated by capsaicin-insensitive afferent fibers in the DPN.

Protective effect of the daming capsule on impaired baroreflexes in STZ-induced diabetic rats with hyperlipoidemia.

BACKGROUND: The Daming capsule (DMC) is a traditional Chinese medicine used to treat hyperlipoidemia. Both clinic trials and studies on animal models have demonstrated that DMC is beneficial against diabetic symptoms. Impairment of the baroreflex can cause life-threatening arrhythmias and sudden cardiac death in patients with diabetes mellitus (DM). This study was designed to elucidate the effects of DMC on baroreflexes in streptozocin (STZ)-induced diabetic rats with hyperlipoidemia. METHODS: Wistar rats were randomly divided into three groups: untreated controls, rats pretreated STZ and high lipids (a diabetes model or DM rats), and DM rats treated with DMC. The baroreflex sensitivity was examined during intravenous injection of phenylephrine (PE) or sodium nitroprusside (SNP) and quantified by the change in heart rate over the change in mean arterial blood pressure (ΔHR/ΔMABP). Morphological remodeling of baroreceptors was analyzed by transmission electron microscopy (TEM). The mRNA levels and expression of GluR2 and a GABAA receptor subunit were measured by quantitative RT-PCR and Western blotting. RESULTS: Compared to untreated DM rats, DMC significantly elevated the ratio of ΔHR/ΔMABP by enhancing the compensatory reduction in HR (-ΔHR) in response to PE-induced hypertension (+ΔMABP) (P < 0.05). In the presence of SNP, DMC increased the ΔMABP (P < 0.05). In addition, DMC markedly shortened the duration of blood pressure changes elicited by PE or SNP in DM rats compared to the untreated DM group (P < 0.05). Electron microscopy revealed disrupted myelin sheaths, swollen ER, and lysed mitochondria in the nucleus ambiguous (NAm) DM rats. These signs of neuropathology were largely prevented by treatment with DMC for 30 days. Treatment with DMC elevated both mRNA and protein level of GluR2 in the NAm of DM rats, but had no effect on GABAA receptor expression. CONCLUSION: The Daming capsule partially reversed the parasympathetic baroreflex impairment observed in STZ-induced diabetic rats with hyperlipoidemia. Treatment with DMC also prevented the degeneration of neurons and myelinated axons in the brain stem NAm and reversed the down-regulation of GluR2 mRNA. Rescue of NAm function may contribute to the medicinal properties of DMC in diabetic rats.

Enhanced baroreceptor control of the cardiovascular system by polyunsaturated Fatty acids in heart failure patients.

OBJECTIVES: The intention of this study was to test the hypothesis that, in heart failure patients, dietary supplementation of polyunsaturated fatty acids (PUFA) enhances arterial baroreceptor control of the cardiovascular system. BACKGROUND: Administration of PUFA reduces the risk of life-threatening arrhythmias in patients surviving myocardial infarction. This might result from potentiation of arterial baroreflexes, but whether or not PUFA enhance baroreflex function has never been studied in humans. METHODS: Patients with post-myocardial infarction left ventricular dysfunction underwent beat-to-beat blood pressure (BP) (Finapres, Ohmeda Inc., Englewood, Colorado) and R-R interval (electrocardiogram) recording; baroreceptor reflexes were assessed from the bradycardic and depressor responses to graded neck suction (NS) as well as by computation of the alpha "spontaneous" baroreflex sensitivity index. Assessments were repeated after prolonged treatment with PUFA (2 g/die, n = 15) or placebo (n = 10). RESULTS: Baseline BP and R-R interval were unaffected by PUFA. Both reflex depressor and bradycardic responses to NS increased after PUFA (respectively from -0.09 +/- 0.01 to -0.16 +/- 0.01 mm Hg x mm Hg(-1), p < 0.01, and from 1.25 +/- 0.9 to 1.76 +/- 1.1 ms x mm Hg(-1), p < 0.04) but not after placebo. The spontaneous baroreflex sensitivity increased in the PUFA (from 8.99 +/- 1.4 to 12.2 +/- 1.2 ms x mm Hg(-1), p < 0.02) but not in the placebo group. Polyunsaturated fatty acids (but not placebo) treatment also significantly increased R-R interval total variance and low-frequency and high-frequency spectral powers. CONCLUSIONS: Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure.

Short-term administration of growth hormone (GH) lowers blood pressure by activating eNOS/nitric oxide (NO)-pathway in male hypophysectomized (Hx) rats.

BACKGROUND: The aim of the study was to evaluate the acute and continuous (up to 14 days of treatment) effect of growth hormone (GH) on blood pressure (BP) regulation and to investigate the interplay between GH, nitric oxide (NO) and BP. In un-supplemented and GH supplemented hypophysectomized (Hx) male rats as well as intact rats, continuous resting mean arterial blood pressure (MAP) was measured using telemetry. Baroreceptor activity and the influences of NO on BP control were assessed during telemetric measurement. Furthermore, basal plasma and urine nitrate levels and aortic endothelial nitric oxide synthase (eNOS) expression were analysed. Endothelial function as well as vascular structure in the hindquarter vascular bed was estimated using an in vivo constant-flow preparation. RESULTS: Hypophysectomy was associated with decreased MAP (Hx: 83 +/- 3 vs Intact: 98 +/- 6 mmHg, p < 0.05) and heart rate (HR) (Hx: 291 +/- 4 vs Intact: 351 +/- 7 beat/min, p < 0.05). Endothelial dysfunction and reduced vasculature mass in the hindquarter vascular bed was found in Hx rats. GH substitution caused a further transient decrease in MAP and a transient increase in HR (14% and 16% respectively, p < 0.05). The reduction in MAP appeared to be NO dependent. Aortic eNOS expression was unchanged. GH substitution resulted in an impaired baroreceptor function. Two weeks of GH treatment did not normalise the BP, vascular structure and the endothelial function in the resistance vessels. CONCLUSION: GH substitution seems to have a short lasting effect on lowering blood pressure via activation of the NO-system. An interaction between GH, NO-system and BP regulation can be demonstrated.

Nitric oxide reduces blood pressure in the nucleus tractus solitarius: a real time electrochemical study.

Increasing evidence has demonstrated that nitric oxide (NO) is involved in central cardiovascular regulation. In this study, we directly measured extracellular NO levels, in real-time, in the nucleus tractus solitarius (NTS) of anesthetized cats using Nafion/Porphyrine/o-Phenylenediamine-coated NO sensors. We found that local application of L-arginine (L-Arg) induced NO overflow in NTS and hypotension. These responses were potentiated in the vagotomized animals. Pretreatment with NO synthase (NOS)/guanylate cyclase inhibitor methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one or NO scavenger hemoglobin attenuated L-Arg-induced hypotension, suggesting that exogenous supplement of NO suppressed cardiac functions through the NOS/cyclic guanosine monophosphate mechanism. The role of endogenous NO was examined after local application of N(G)-nitro-L-arginine methyl ester (L-NAME). We found that L-NAME suppressed endogenous NO levels in NTS and elicited hypertension and tachycardia. Taken together, our data suggest that NO is tonically released in the NTS to inhibit blood pressure.

Comparative effects of mibefradil and nifedipine gastrointestinal transport system on autonomic function in patients with mild to moderate essential hypertension.

BACKGROUND: L-type dihydropyridine calcium channel blockers (CCBs) have been implicated in increased cardiovascular events in patients with hypertension, perhaps due to adverse effects on autonomic nervous system (ANS) function. Blockade of T-type calcium channels may limit ANS dysfunction by inhibition of T channel-mediated neuroendocrine effects. OBJECTIVE AND DESIGN: This double-blind, parallel group study compared the effect of nifedipine gastrointestinal transport system (GITS) (L-type CCB) versus mibefradil (T-type CCB) on ANS function in patients with mild-moderate essential hypertension. METHODS: Sixteen patients (10 male, 6 female; age 57.2 +/- 2.3 years), diastolic blood pressure (DBP) < 95 mmHg were randomized to nifedipine 30 mg daily or mibefradil 50 mg daily (2 weeks), then nifedipine 60 mg daily or mibefradil 100 mg daily (4 weeks). Sympathetic nervous system activity (SNSA) was assessed using norepinephrine kinetics. Parasympathetic nervous system activity (PSNA) was assessed from 24 h Holter recordings of heart rate variability (HRV). Non-invasive baroreflex sensitivity (BRS) provided integrated assessment of ANS. RESULTS: Patient groups were well matched at baseline. Achieved DBP was lower in patients treated with mibefradil compared with nifedipine, (83.4 +/- 1.7 versus 95.25 +/- 3.3 mmHg). There were no significant differences in SNSA and BRS between groups, however the root mean square of successive differences and high frequency power (HFP) were increased in mibefradil compared with nifedipine-treated patients [(+ 1.07 +/- 1.6 versus -3.36 +/- 1.2 ms, P < 0.05) and (+ 0.28 +/- 0.1 versus -0.23 +/- 0.1 ms2, P < 0.01), respectively]. Furthermore, Ln HFP/Ln total power was increased from week 0 to week 6 in the mibefradil-treated group, (0.71 +/- 0.02 versus 0.74 +/- 0.03, P = 0.046). CONCLUSION: No differences existed between effect of L- and T-type CCBs on SNSA and BRS. However, T-type CCBs increased PSNA, independent of achieved changes in heart rate.

Effects of long-term vasodilator therapy in patients with carotid sinus hypersensitivity.

BACKGROUND: In patients affected by carotid sinus hypersensitivity, long-term vasodilator therapy might increase the risk of syncopal episodes by reducing systolic blood pressure and venous return to the heart. METHODS AND RESULTS: Thirty-two patients (mean age 73 +/- 9 years; 20 men) who met all the following criteria were included: (1) one or more episodes of syncope occurring during long-term (>6 months) treatment with angiotensin-converting enzyme inhibitors, long-acting nitrates, calcium antagonists, or a combination of these; (2) a positive response to carotid sinus massage, defined as the reproduction of spontaneous syncope in the presence of ventricular asystole > or =3 seconds or a fall in systolic blood pressure > or =50 mm Hg; (3) negative workup for other causes of syncope. The patients were randomly assigned to continue or to discontinue use of vasodilators; carotid sinus massage was repeated 2 weeks after randomization. By the end of the study period, the baseline values of systolic blood pressure were significantly different between the 2 groups of patients both in supine (P=.01) and upright (P=.03) positions. Syncope had been induced by carotid sinus massage in 81% of patients in the "on-vasodilator" group and in 62% of patients in the "off-vasodilator" group (P=.21). The cardioinhibitory reflex was of similar magnitude in the 2 groups, being found in 50% of the patients in each group, with a maximum ventricular pause of 7.1 +/- 2.7 and 6.7 +/- 1.8 seconds, respectively. The percentage decrease of blood pressure did not differ between the 2 groups, even if, in absolute values, the baseline difference of blood pressure roughly persisted for the duration of the test. In consequence of that, the rise of blood pressure to similar values was delayed approximately 30 seconds in the "on-vasodilator" group and took more than 2 minutes to return to baseline values. CONCLUSIONS: In patients affected by carotid sinus hypersensitivity, chronic vasodilator therapy does not have a direct effect on carotid sinus reflexivity, although the delayed recovery of pretest blood pressure values could indirectly potentiate the severity of the clinical manifestations of the syndrome. The persistence of hypotension for a longer time after the end of the massage suggests that vasodilators cause an impairment of compensatory mechanisms.

Ouabain produces diverse excitatory effects on afferent baroreceptor nerve activity in SHR and WKY animals.

The effect of acute ouabain treatment was evaluated on afferent baroreceptor nerve activity in spontaneously hypertensive rats (SHR) compared with Wistar Kyoto rats (WKY). Under urethane anesthesia (1.2 mg/Kg) the discharge of the recurrent laryngeal nerve was utilized as index of arterial baroreceptor activity (BNA) in rats with the ipslateral vagus cut at a proximal level. The ouabain (30 micrograms, i.v.) treatment produced an excitatory effect on BNA without changes in basal arterial pressure in both groups studied. This effect was larger in SHR (92 +/- 10%) than WKY (37 +/- 4%, P < 0.01). The arterial pressor response to phenylephrine was similar in both SHR and WKY before (20 +/- 1 and 22 +/- 1.2 mmHg) and after (18 +/- 1.4 and 20 +/- 2 mmHg, respectively) ouabain. The BNA under phenylephrine-induced peaks of high arterial pressure was significantly higher in SHR (61 +/- 15%) than in WKY (41 +/- 5% P < 0.01) but after ouabain treatment the opposite was observed (31 +/- 5 vs. 61 +/- 4% P < 0.01). The inhibitory effects of sodium nitroprusside on arterial pressure and BNA were similar in SHR and WKY groups both before and after the ouabain treatment. These data indicate an excitatory effect of ouabain on baroreceptor nerve activity in normotensive and markedly in hypertensive rats which could contribute to the reflex arterial pressure regulation, besides the known inotropic action on the heart.

Antihypertensive effect of corilagin in the rat.

The antihypertensive effect of corilagin, one of the ellagitannins purified from the seeds of Euphoria longana Lam. (Sapindaceae), was investigated in the spontaneously hypertensive rat (SHR). Administration of corilagin into conscious SHR at 5 mg/kg produced an antihypertensive effect equivalent to that induced by 1 mg/kg of guanethidine. This dose-dependent hypotensive effect was comparable with that observed in anesthetized SHR animals. Corilagin did not modify the baroreflex sensitivity in phenylephrine-challenged SHR. Corilagin reduced plasma noradrenaline in a dose-dependent fashion, an effect that was maintained in adrenalectomized rats. Failure of the antagonists for alpha2-adrenoceptors, idazoxan and yohimbine, as well as for dopamine receptors, haloperidol and domperidone, to reverse the antihypertensive actions of corilagin ruled out the participation of these receptors. Moreover, corilagin attenuated the pressor effects of methoxamine and Bay K8644 to a similar degree, indicating the direct effect of corilagin on vascular activity in rats. These results suggest that corilagin possesses the ability to lower blood pressure through the reduction of noradrenaline release and (or) direct vasorelaxation.

Inhibition of catecholamine (noradrenaline, dopamine) release in the locus coeruleus and the hypothalamus by baroreceptor activation: identification of the involved baroreceptors.

We have previously shown that experimentally induced blood pressure changes modify the release rates of catecholamines in the hypothalamus and the locus coeruleus. The aim of the present investigation was to identify the peripheral baroreceptors and the centripetal pathways responsible for the changes of catecholamine release in these brain areas. In anaesthetized cats, push-pull cannulae were bilaterally inserted into the locus coeruleus and the posterior hypothalamus. The two brain areas were superfused simultaneously with artificial cerebrospinal fluid. Baroreceptor activation by phenylephrine-induced blood pressure elevation decreased the release rate of noradrenaline in the locus coeruleus and the release rates of noradrenaline and dopamine in the posterior hypothalamus. Similar effects were elicited by electrical stimulation of the central trunk of the transected vagus and aortic depressor nerves (vagus-ADN). Transection of the nerves abolished the effect of phenylephrine on the release of noradrenaline in the locus coeruleus. Nerve transections attenuated slightly the decreased release of noradrenaline elicited by phenylephrine in the posterior hypothalamus, while the reduced dopamine release rate was not influenced. The selective stimulation of baroreceptors in the carotid sinus by an inflatable catheter did not influence the release of catecholamines in the locus coeruleus, while release rates of noradrenaline and dopamine in the posterior hypothalamus were decreased. The simultaneous superfusion of locus coeruleus and hypothalamus revealed that, in both areas, noradrenaline release is inhibited by baroreceptor activation. Noradrenergic neurons of the posterior hypothalamus are inhibited by baroreceptor impulses conducted by the carotid sinus nerve and vagus-ADN, while the noradrenergic neurons of the locus coeruleus seem to respond to impulses transmitted by vagus-ADN.(ABSTRACT TRUNCATED AT 250 WORDS)

A potential role of central A1 adenosine receptors in the responses to hypothalamic stimulation in the anaesthetized cat.

In pentobarbitone anaesthetized and paralysed cats the effects of the A1 adenosine antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) have been observed on the pressor response to stimulation of the hypothalamic defence area (HDA) and on the effects of baroreceptor and chemoreceptor reflex activation on arterial blood pressure. The administration of DPCPX decreased the magnitude of the HDA pressor response and the chemoreceptor induced rise in blood pressure. The fall in blood pressure induced by baroreceptor activation was enhanced to a small yet significant extent. No changes were observed in the tachypnoea evoked by hypothalamic defence area (HDA) stimulation. These results suggest a possible role for central adenosine A1 receptors in mediating the cardiovascular changes evoked during HDA stimulation.

Basal and reactive plasma catecholamine levels under stress and anesthesia in rabbits.

The present study was undertaken to determine if electrical stimulation of the hypothalamic defense area (HDA) and baroreflex activation elicited by head up body tilt produced changes in plasma catecholamine (CA) levels in anesthetized rabbits. We also compared the effects of two anesthetics, isoflurane and sodium pentobarbital, upon basal and reactive CA levels, and upon autonomic reactivity. HDA stimulation was found to produce significant increases in plasma norepinephrine (NE) levels but not epinephrine (E) levels. Passive tilt was found to produce statistically significant increases in NE levels for both anesthetics used and a significant increase in E levels for animals anesthetized with isoflurane. Basal and reactive measurements provided evidence that pentobarbital has a more suppressive effect upon the autonomic nervous system than isoflurane: (a) Basal NE levels were significantly lower in pentobarbital anesthetized animals than in isoflurane-anesthetized animals; and (b) Baroreceptor sensitivity to a passive tilt stressor was significantly higher for animals anesthetized with isoflurane than for animals anesthetized with pentobarbital.

Vascular versus myocardial effects of calcium antagonists.

As vascular smooth muscle tone and myocardial contractility both depend on calcium entry, the calcium antagonists are not only potent arterial vasodilators, but may also have important negative inotropic effects. For example, verapamil is nearly equipotent in reducing vascular smooth muscle tone and myocardial contraction in isolated tissue preparations. In contrast, felodipine has high vascular selectivity in such preparations, and drug concentrations required to depress myocardial contraction are more than 100 times greater than those required to relax vascular smooth muscle. In the isolated, isovolumetrically contracting canine left ventricle, clinically relevant concentrations of felodipine (14 nmol/L) produce coronary vasodilation and a mild positive inotropic response. Using left ventricular (LV) pressure-volume analysis, we evaluated a similar dose of felodipine (plasma drug concentration 16 nmol/L) in conscious dogs. Felodipine produced a 25mm Hg fall in arterial pressure and a 10% reduction in peripheral vascular resistance. There was no negative inotropic effect. Instead, myocardial contractile performance was slightly but significantly enhanced. These results were not altered by adrenergic blockade. Further studies in our laboratory showed that doses of amlodipine and nifedipine producing arterial vasodilation of a magnitude similar to that produced by felodipine had negative inotropic effects in the conscious dog. Only felodipine enhanced the rate of LV relaxation and the rate of early diastolic filling. Thus, felodipine was significantly more vasoselective than amlodipine and nifedipine. The direct inotropic effects of calcium antagonists are difficult to evaluate in clinical studies because of the load-dependence of most conventional measures of LV performance. However, no negative inotropic effects are clinically relevant doses of felodipine have been identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Augmented neuronal activity in the hypothalamus of spontaneously hypertensive rats.

Previous studies indicate a tonic GABAergic inhibitory mechanism in the posterior hypothalamus (PH) contributes to modulating cardiovascular activity. Blockade of GABA receptors on neurons in this area elicits an increase in sympathetic discharge, arterial pressure, and heart rate. It has been proposed that a deficit in this inhibitory system may be responsible for the elevated pressure in the spontaneously hypertensive rat (SHR). The purpose of this study was to determine if the spontaneous neuronal activity in the posterior hypothalamus of spontaneously hypertensive rats differs from that of age-matched normotensive Wistar-Kyoto rats (WKY). Single unit, extracellular recordings of posterior hypothalamic neurons were performed on both in vivo and in vitro preparations. The spontaneous firing rate of posterior hypothalamic neurons in the anesthetized adult SHR was significantly higher (3.66 +/- 0.55 Hz) compared to that of the anesthetized adult WKY rat (2.11 +/- 0.29 Hz). Moreover, more of the neurons in the anesthetized SHR (38%) had a bursting discharge pattern than in the WKY (16%). In order to exclude inputs from peripheral receptors or other brain areas, an in vitro preparation was used. Neurons from both young and adult SHRs also had an increased spontaneous discharge rate and higher percentage of burster-type cells in the posterior hypothalamus compared to neurons from age-matched WKYs in the brain slice preparation. Both the in vivo and in vitro findings support the possibility that an elevated neuronal activity in the posterior hypothalamus, a known pressor area, of the SHR contributes to the development and/or maintenance of hypertension in this animal model.

Sympathetic activation by chronic insulin treatment in conscious rats.

Normal male Wistar rats pretreated with insulin for 12 days were studied to determine if chronic insulin treatment would reproduce the cardiovascular changes occurring in obese rats with hyperinsulinemia. After 12 days, plasma insulin rose while plasma glucose fell, but basal pressures recorded while the rats were awake remained unchanged. Depressor and tachycardic responses to isoproterenol were enhanced, thereby suggesting that beta adrenergic responsiveness had been increased. By contrast, cardiovascular responses to angiotensin were unaltered. The same rats were then anesthetized with urethane-chloralose, and reflex responses, elicited by elevating blood pressure with phenylephrine or lowering it with sodium nitroprusside, were compared with those from control rats that had not been treated with insulin. Reflex inhibition of splanchnic nerve activity during phenylephrine infusion was weaker, whereas reflex tachycardia during nitroprusside infusion was stronger in insulin-treated rats. However, cardiovascular and sympathetic responses elicited by electrical stimulation of the posterior hypothalamus were the same whether the rats had been treated with insulin or not. Although these differences imply that hyperinsulinemia cannot be solely responsible for the cardiovascular dysfunction in obesity, our results nonetheless suggest that by increasing beta adrenergic responsiveness and reducing sympathetic inhibition, excess insulin can cause sympathetic predominance even without elevating blood pressure.

Pressor actions of arginine vasopressin in pithed Sprague-Dawley, Wistar-Kyoto and spontaneously hypertensive rats before and after treatment with nifedipine or pertussis toxin.

The pressor actions of arginine vasopressin (AVP) were examined in pithed Sprague-Dawley and Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Prior to pithing, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded via an intra-arterial catheter from sodium pentobarbital anaesthetized rats. SBP and DBP recorded from SHR were significantly greater than those from Sprague-Dawley and WKY rats. However, after pithing, there were no significant differences between DBP among the various strains. Pertussis toxin pretreatment significantly reduced the prepithing SBP and DBP of the SHR but not Sprague-Dawley or WKY rats. Administration of nifedipine significantly reduced DBP of pithed rats. The dose-diastolic pressure response curves obtained from infusion of AVP in Sprague-Dawley and WKY rats were not significantly different from one another, but the maximal vasopressor responses to AVP in pithed SHR were enhanced. Administration of nifedipine to Sprague-Dawley and WKY rats did not affect the dose-response curve to AVP, but nifedipine administration in SHR led to a significant inhibition of the pressor responses to AVP. Furthermore, pertussis toxin pretreatment of rats significantly reduced a component of the AVP pressor effect in SHR but not Sprague-Dawley or WKY rats. We speculate that, in SHR, vasopressin receptors are coupled to a pertussis toxin-sensitive G protein that, in turn, may couple to a dihydropyridine-sensitive calcium channel and also to a pertussis-insensitive G protein that is probably coupled to the phospholipase C/intracellular calcium release process. A component of the elevated blood pressure in SHR is also regulated by a pertussis toxin-sensitive process.(ABSTRACT TRUNCATED AT 250 WORDS)

Nifedipine versus fentanyl to prevent the pressor response to tracheal intubation.

Thirty six patients, ASA I or II, undergoing surgery that required tracheal intubation, were allocated randomly into three groups of twelve. Before induction of anesthesia, they received either saline, nifedipine sublingual 10 mg or fentanyl 1.5 micrograms.kg-1 i.v. Heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure (MAP) were recorded automatically every minute for 5 minutes before induction of anesthesia, and for 5 minutes after intubation. Nifedipine was better than fentanyl in blocking the pressor response to intubation. The fentanyl dose was too small to abolish this response completely. The increase in HR and blood pressure were most evident in the control group, followed by fentanyl, and the least increase was seen with nifedipine.

Omega-conotoxin GVIA, the N-type calcium channel inhibitor, is sympatholytic but not vagolytic: consequences for hemodynamics and autonomic reflexes in conscious rabbits.

We investigated the effects of the N-type calcium channel blocking agent, omega-conotoxin GVIA, on the resting hemodynamics and on some autonomic reflexes in the conscious rabbit. omega-Conotoxin 3 and 10 micrograms/kg i.v. reduced mean arterial blood pressure by 16 +/- 2 and 25 +/- 3 mm Hg, respectively, over 30 min accompanied by a tachycardia. Renal vascular conductance (Doppler flowmeter) increased by 27.6 +/- 3.7 and 38.6 +/- 10.3% at 30 min after omega-conotoxin 3 and 10 micrograms/kg, respectively. Vasodilatation was also observed but to a lesser extent in the hindquarter and mesenteric vascular beds. The baroreceptor-heart rate reflex was evoked by a drug method (bolus injection of sodium nitroprusside and phenylephrine) and by inflation of perivascular balloons implanted on the thoracic vena cava and aorta. omega-Conotoxin (3 micrograms/kg) abolished the sympathetic component of the cardiac baroreceptor reflex without affecting vagal efferent activity. In addition, marked vagal-mediated bradycardia from (a) the "Bezold-Jarisch-like" reflex evoked by serotonin (1-10 micrograms/kg i.v.) and (b) the nasopharyngeal reflex evoked by cigarette smoke were unaffected by omega-conotoxin (3-10 micrograms/kg). We conclude that omega-conotoxin-induced N-type calcium channel blockade abolishes sympathetic but not vagal cardiac efferent activity. The hypotension and peripheral vasodilatation are probably due to the prejunctional sympatholytic action of the peptide. These N-type calcium channels are thus limited to the sympathetic varicosities in the rabbit.

Involvement of the A1 cell group in baroreceptor inhibition of neurosecretory vasopressin cells.

Extracellular recording experiments were done to investigate the proposal that arterial baroreceptor inhibition of vasopressinergic (AVP) neurosecretory cells involves the A1 noradrenaline cell group of the caudal medulla. The responsiveness of functionally identified AVP cells of the rat supraoptic nucleus to baroreceptor activation was not discernibly altered by A1 region lesions even though AVP cell responses to certain other stimuli were abolished. Acute blockade of A1 region function by injection of gamma-aminobutyric acid sometimes impaired AVP cell responsiveness to baroreceptor stimulation, although more commonly there was no effect. These data suggest that the A1 cell group is not an essential component in pathways mediating baroreceptor inhibition of neurosecretory AVP cells, but may contribute to the sensitivity of AVP cells to this input.