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Biomedical subjects

R Pedrinelli

Publications and source records attributed to R Pedrinelli.

At least 109 records · Page 6Linked to original sources
PubMed1986

Renal vein renin in renovascular hypertension: the experience of two Italian centers.

A retrospective analysis of renal vein renin results has been done in 96 patients with renal artery stenosis and hypertension studied in two Italian centers (Sassari and Pisa) with respect to the outcome of either surgery or percutaneous transluminal angioplasty (PTA). In all patients the renal vein renin ratio and the V-A/A ratios for the affected and unaffected kidney were calculated. Each patient underwent surgery (75) of PTA (21): 71 subjects were cured, 17 improved whereas the arterial pressure did not vary after revascularisation procedure in 8 patients. In the Pisa series all 54 patients showed a lateralisation with contralateral renin suppression and 95% of them benefitted from surgery. In the Sassari series 42 patients were submitted to PTA or surgery, not only on the basis of a positive renal vein renin study but taking into account a complete clinical evaluation: 8 of them were cured or improved in spite of negative renal vein renin criteria. In the two series, the better predictive index appeared to be the suppression of the renin secretion from the contralateral kidney while the high/low renin ratio showed a consistent amount of false-positive and false-negative results. Our retrospective study demonstrates that the renal vein test in hypertensive patients with renal artery stenosis is highly predictive of the curability of the disease, particularly when contralateral suppression of renin secretion is present. On the other hand, since patients with negative renin indexes can also take benefit from surgery of PTA, the renin parameters cannot be adopted as the sole criterion in making the decision to operate.

Adult↗
PubMed1986

Vascular responses to ouabain and norepinephrine in low and normal renin hypertension.

A circulating Na+, K+-ATPase inhibitor may cause arterial hypertension in patients with suppressed plasma renin activity, either directly or by sensitizing peripheral vessels to alpha-adrenergic stimulation. This hypothesis was tested by evaluating forearm arteriolar (plethysmographic technique) response to exogenous alpha-adrenergic stimulation by a 2-minute intra-arterial infusion of norepinephrine (0.1 microgram/dl tissue per minute) and to Na+, K+-ATPase inhibition by sequential 20-minute intra-arterial infusions of ouabain (0.36 and 0.72 microgram/dl tissue per minute). Two groups of hypertensive subjects with suppressed plasma renin activity, either essential or secondary to aldosterone excess, were compared with age-matched and sex-matched hypertensive subjects with normal plasma renin activity (n = 7 per group). No significant differences in forearm vascular response to norepinephrine were found among the three groups. Ouabain caused a highly significant, dose-related increment in forearm vascular resistance that was not accompanied by changes in the contralateral limb or systemic blood pressure. No significant interindividual differences in vascular responsiveness to ouabain were found. The individual increments in forearm vascular resistance during ouabain administration were unrelated to basal values or to plasma aldosterone, norepinephrine, or potassium concentrations. These data are not consistent with the hypothesis that suppressed basal Na+, K+-ATPase activity is primarily a characteristic of hypertensive patients with unresponsive plasma renin activity. Overall, these results cast doubts on the possibility of linking the development of human low renin hypertension to an endogenous Na+, K+-ATPase inhibitor.

Adult↗
PubMed1986

Verapamil antagonizes forearm vasoconstriction mediated by selective alpha 1- and alpha 2-agonists in hypertensive patients.

Calcium channel blocking agents preferentially antagonize alpha 2-mediated pressor responses in various animal species. Whether the same happens in man is not clear. For this reason we studied the interference exerted by verapamil, a calcium entry blocker, on forearm vasoconstriction mediated by selective alpha 1- (methoxamine) and alpha 2- (B-HT 933) adrenergic agonists in untreated mild-to-moderately hypertensive patients (n = 22). Each patient underwent a single study. Forearm blood flow was recorded by strain gauge venous plethysmography; all drugs were infused into the brachial artery at systemically ineffective rates. Cumulative dose-response curves to intra-arterial methoxamine or B-HT 933 were obtained during saline or two different rates of verapamil infusion (0.9 and 3.1 micrograms/100 ml forearm tissue per min) which increased forearm blood flow dose-dependently without changing systemic blood pressure or heart rate. Either methoxamine or B-HT 933 decreased forearm blood flow during saline infusion, but their effect was blunted in a dose-dependent manner during verapamil. No evidence of preferential alpha 2-antagonism was present. At variance with animal data, calcium entry blockade by verapamil antagonizes either alpha 1- or alpha 2-mediated vasoconstriction in human forearm vessels.

Adrenergic alpha-Agonists↗
PubMed1985

Multicentre comparison of the antihypertensive effect of acebutolol and hydrochlorothiazide in uncomplicated mild-moderate hypertension in the elderly.

To evaluate the efficacy of acebutolol, 400-600 mg/day in elderly hypertensive patients, and to compare it with hydrochlorothiazide 25-50 mg/day, 45 patients with mild-moderate uncomplicated hypertension were treated for 6 weeks in a multicentre, single-blind, randomized, crossover trial. Acebutolol decreased supine systolic blood pressure from 186.5 to 162.7 mmHg and diastolic blood pressure from 107.4 to 92.4 mmHg. Hydrochlorothiazide decreased systolic blood pressure from 185.0 to 166.4 and diastolic blood pressure from 107.2 to 96.4. There was no difference between the effects of acebutolol and hydrochlorothiazide on blood pressure during the trial. Both drugs proved to be safe and effective antihypertensive agents, provided the major contraindications for their use were taken into account. Beta-blockade by acebutolol was highly effective in treating mild-moderate arterial hypertension in the elderly.

Acebutolol↗
PubMed1985

Calcium entry blockade and alpha-adrenergic responsiveness in vivo.

In an initial series of studies in pithed normotensive rats, nitrendipine (3, 10, 30 micrograms/kg/min X 15 min) preferentially antagonized the pressor responses to BHT 920, a selective alpha 2-adrenergic agonist, while hardly interfering with responses to methoxamine, a selective alpha 1-agonist. The preferential alpha 2-antagonism by nitrendipine (0.01-0.3 mg/kg i.v.) was also shown by its greater antagonism of pressor responses to norepinephrine in propranolol (1 mg/kg)-prazosin (0.3 mg/kg i.v.)-pretreated pithed rats (alpha 1-receptors blocked, alpha 2 exposed) than in propranolol-yohimbine (0.3 mg/kg)-pretreated preparations (alpha 2 blocked, alpha 1 exposed). However, the effect of nitrendipine on vascular alpha 2-adrenergic responsiveness was found to be not specific for calcium entry blockers (CaEB) since vasodilators without calcium entry blocking properties [sodium nitroprusside (3-30 mg/kg/min X 15 min) and hydralazine (0.03-3.0 mg/kg/min X 15)], gave the same pattern of interference with pressor responses to methoxamine and BHT 920 in exactly the same model. Both vasodilators depressed the pressor dose-response curves to BHT 920, while sparing those to methoxamine. Thus, calcium entry blockade preferentially antagonized alpha 2-mediated vasoconstriction, but this effect was common to other non-CaEB vasodilators. The reason for the relative sparing by CaEB of pressor responses to alpha 1-adrenergic stimulation was sought in a second series of studies of dose-response curves to methoxamine following partial alpha-adrenoceptor inactivation by phenoxybenzamine (0.3 mg/kg i.v.). In these conditions, nitrendipine (30 micrograms/kg/min), sodium nitroprusside (30 micrograms/kg/min), and hydralazine (3 mg/kg/min) all strongly depressed the pressor responses to methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Influence of food on acute and chronic effects of captopril in essential hypertensive patients.

To determine if food reduces the hemodynamic and humoral effects of captopril in patients with essential hypertension, we performed two studies. In the acute study, 15 inpatients with uncomplicated essential hypertension randomly received a single oral dose of placebo or captopril (25 mg) while fasting or after eating, or captopril (50 mg) after eating. Blood pressure and heart rate were measured every 30 min up to 4 h (and up to 10 h in six out of the 15 patients), while plasma renin activity, plasma aldosterone, and serum angiotensin-converting enzyme were measured 2 h after dosing. Compared with placebo, captopril significantly reduced mean blood pressure (p less than 0.001), serum angiotensin-converting enzyme (p less than 0.005), and aldosterone (p less than 0.001), increased plasma renin activity (p less than 0.05), and did not change heart rate; there was no difference between the fasting and the fed state. In the six patients followed up to 10 h, captopril both before and after food significantly and similarly reduced mean blood pressure up to 8 h (p less than or equal to 0.05). In the chronic study, 10 patients with uncomplicated essential hypertension, while having prolonged (3-12 months) treatment with captopril (50 mg twice a day), were asked to take captopril for 1 month 1 h before eating and for another month during or immediately after eating. The sequence was randomized, and blood pressure, heart rate, plasma renin activity, serum angiotensin-converting enzyme, and plasma aldosterone were measured at the end of each period 12 h after last dosing.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Naloxone inhibits sulpiride-induced hyperprolactinaemia in man.

In order to evaluate the interaction between the opiate-like peptidergic pathways and the dopaminergic system in modulating prolactin (PRL) secretion, ten normal volunteers were studied according to a double-blind, cross-over, randomized experimental design. A group of five subjects was given a fixed dose of sulpiride (a selective antidopaminergic agent, 25 mg i.v.) plus either placebo or three different doses of naloxone (a selective opioid antagonist, 0.2, 0.4, 0.8 mg i.v.) while a second group of five subjects received the same drugs in a 'reverse' protocol, i.e. a fixed dose of naloxone (0.4 mg i.v.) plus either placebo or increasing doses of sulpiride (25, 50, 100 mg i.v.). In both groups, the drugs were injected simultaneously and blood samples for PRL determination were taken at various intervals during the 15 min preceding drug injections and then over the following 4 h. Naloxone (0.4 mg i.v.) per se did not induce any modification of plasma PRL levels, but reduced to a significant extent sulpiride-induced hyperprolactinaemia (P less than 0.02). However, a higher dose of naloxone (0.8 mg i.v.) did not cause significant changes in sulpiride-stimulated PRL levels. Increasing dosages of sulpiride (up to 100 mg i.v.) reversed the blunted response of PRL after sulpiride, 25 mg, in presence of naloxone. Our data show that naloxone, at a dose of 0.4 mg i.v. inactive per se on basal PRL levels, is able to blunt significantly sulpiride-induced hyperprolactinaemia. This suggests that, in man, opioid peptides are able to influence PRL release after antidopaminergic stimuli.

Adolescent↗
PubMed1985

Humoral and haemodynamic interactions between clonidine and nifedipine in human essential hypertension.

Acute administration of nifedipine (NIF), a calcium entry blocker (CEB), in animals reduces the hypotensive effect of clonidine (CLN), an alpha-adrenergic agonist. In order to evaluate possible negative interactions between NIF and CLN in man during chronic treatment with these drugs, 12 patients with mild to moderate uncomplicated essential hypertension received either NIF (20 mg twice daily), CLN (0.25 mg once daily), the two drugs together at the same doses, or their matched placebos for a 2-week period each. NIF (-13.5% versus placebo) and CLN (-10.2% versus placebo) decreased blood pressure significantly and when combined, blood pressure was further decreased (-17.1% versus placebo). Heart rate was increased by NIF and NIF + CLN but unchanged by CLN alone. Plasma renin activity (PRA) tended to increase with NIF, decreased with CLN (P < 0.05) and was unchanged with NIF + CLN. Plasma aldosterone did not vary during any of the phases of the trial. These results indicate that NIF and CLN do not interact negatively on blood pressure control in essential hypertensive subjects.

Clonidine↗
PubMed1985

Calcium entry blockade by nitrendipine and alpha adrenergic responsiveness in vivo: comparison of systemic vs. local effects.

Calcium entry blockade in vivo preferentially antagonizes systemic pressor responses to alpha-2 adrenergic agonists, whereas relatively sparing alpha-1 mediated vasoconstriction; however, in vitro studies have given results discordant from those obtained in vivo. Because of these discrepancies we have compared the effect of calcium entry blockade by nitrendipine on systemic and local (autoperfused hindquarters) pressor responses to selective adrenergic agonists: cirazoline for alpha-1 and B-HT 920 for alpha-2. Pithed, vagotomized, normotensive Sprague-Dawley rats were used. Confirming previous results, nitrendipine (3.0 and 30.0 micrograms/kg/min X 15 min) selectively antagonized the systemic pressor responses to B-HT 920 without affecting significant responses to the alpha-1 agonist. However, in the isolated, autoperfused hindquarters of pithed rats, these same doses of nitrendipine depressed by 36 and 45% the maximum vasoconstrictor response to cirazoline. Because no significant vasoconstrictor response to B-HT 920 could be demonstrated in this same preparation, we induced supersensitivity to the alpha-2 agonist by reserpine pretreatment (0.3 mg/kg X 3 days). Reserpine increased vascular responsiveness to B-HT 920, without modifying its selective alpha-2 agonistic properties, as assessed by the use of selective alpha-1 (prazosin, 0.5 mg/kg i.v.) and alpha-2 (rauwolscine, 0.5 mg/kg i.v.) antagonists and of phentolamine (5 mg/kg i.v.), a nonspecific alpha adrenergic antagonist. After pretreatment with reserpine, nitrendipine antagonized both the B-HT 920-mediated vasoconstriction (by an average of 40 and 57%, respectively) and the cirazoline alpha-1-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1985

Calcium entry blockade by nitrendipine and alpha adrenergic responsiveness in vivo: comparison with noncalcium entry blocker vasodilators in absence and presence of phenoxybenzamine pretreatment.

To investigate the in vivo interaction between calcium entry blockade by nitrendipine (a dihydropyridine calcium entry blocker) and alpha adrenergic-mediated end-organ responsiveness, four series of experiments were carried out in normal Sprague-Dawley rats. In ganglion-blocked rats (hexamethonium, 10 mg/kg i.p. plus atropine, 1.0 mg/kg i.p.), nitrendipine (0.3 mg/kg) antagonized the pressor responses to angiotensin II and vasopressin as well as to norepinephrine, thus indicating the lack of specificity of its antagonism to alpha adrenergic vasoconstriction. The results of the next two series of experiments showed first that, in pithed rats, nitrendipine (0.01 to 0.3 mg/kg) in presence of prazosin shifted the norepinephrine pressor dose-response curves to the right whereas it was ineffective in yohimbine-pretreated animals. These data, suggesting a preferential alpha-2 antagonism by nitrendipine, were confirmed further by its little effect on pressor responses to methoxamine as contrasted with its marked progressive depression of the maximum response to B-HT 920 (about 80% at the highest rate of infusion). However, qualitatively similar results were obtained by the noncalcium entry blocker vasodilators, both sodium nitroprusside and hydralazine, both of which led to minor shifts to the right of the methoxamine pressor dose-response curves, whereas dose-dependently depressing the maximum pressor response to B-HT 920 (about 70 and 40%, respectively). Thus, calcium entry blockade appeared to antagonize preferentially alpha-2-mediated vasoconstriction, but this effect was common to other vasodilators devoid of calcium entry blocking properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Naloxone does not modify the antihypertensive effect of captopril in essential hypertensive patients.

It has been reported that endogenous opioid antagonism through naloxone (NAL) blunts the hypotensive effect of captopril (CAP) in normal man. For this reason a study was carried out to determine whether NAL interacts with the antihypertensive effect of CAP in patients with mild-to-moderate essential hypertension (n = 6; age 22-43 years). Patients received, according to a randomized code, placebo (PL) during saline infusion, CAP (25 mg orally) during saline infusion, PL + NAL (0.4 mg as a bolus followed by a continuous infusion of 4.0 mg/h for 2 h) and CAP + NAL at the same doses. Three-day intervals elapsed between each phase of the study. Blood pressure (BP) and heart rate (HR) were recorded before (-20 to 0 min) and every 15 min for the next 2 h after drug administration. Blood samples for plasma renin activity (PRA), noradrenaline (NA) and aldosterone (ALD) were collected before (time 0) and 120 min after drug administration. Neither PL nor NAL changed any of the parameters examined, while CAP alone reduced mean BP to a highly significant extent. Naloxone did not change the hypotensive effect of CAP to any significant extent. Captropril, either alone or associated with NAL, tended to reduce plasma ALD and increase PRA (P less than 0.05) without changing HR or plasma NA. These data indicate that, at least under the experimental conditions used, endogenous opioid antagonism does not interfere with the haemodynamic and humoral effect of CAP in essential hypertensive man. This suggests that endogenous opioids do not mediate the pharmacological actions of CAP.

Adult↗
PubMed1985

Angiotensin-converting enzyme inhibitors in hypertension: a review.

Angiotensin-converting enzyme (ACE) inhibitors are a new class of drugs, whose main indications are the treatment of hypertension and of heart failure. Data obtained with captopril, the first orally active ACE inhibitor, affords an understanding of the rationale of their therapeutic use based on the knowledge of their mechanisms of action, efficacy, contraindications and precautions, dosage and frequency of administration, side-effects, interactions and advantages. ACE inhibitors appear to exert their haemodynamic effect mainly by inhibiting the renin-angiotensin-aldosterone system, but also by modulating sympathetic nervous system activity and by increasing prostaglandin synthesis. Therefore they act both on vasoconstrictor and volume factors, since they cause vasodilation (the main effect) and mild natriuresis without affecting the heart rate and contractility and, probably, favourably influencing renal, coronary and cerebral circulation. So far it appears that ACE inhibitors can be usefully employed in the treatment of heart failure, in which they reduce both pre- and after-load, and mainly of hypertension. In the past captopril has been used to treat only severe and or resistant hypertension and some secondary forms, like renal parenchymal and renovascular hypertension, but now it seems that captopril is useful also to treat mild to moderate essential hypertension. Their efficacy in reducing blood pressure is similar to that of thiazide diuretics and of beta-blockers, the two drugs now considered of first choice and they exert their hypotensive action without the development of pseudotolerance or tolerance. ACE inhibitors seem, at the moment, contraindicated in pregnancy and in hyperkalaemic syndromes and must be used with caution in patients with collagen disease (mainly associated with renal failure), with severe bilateral renal artery stenosis (and with severe artery stenosis of a solitary kidney) and with severe sodium depletion. It is now established that captopril has a flat dose response curve and that it must be given (twice daily) at a dose not exceeding 150 mg/day. The same pharmacological approach must be used with future ACE inhibitors in order to establish the right posology and the frequency of administration. In this respect enalapril seems to be a promising ACE inhibitor with a prolonged action (at least 24 hours). The exact posology of ACE inhibitors might be crucial, since it has been shown that the side-effects of captopril (skin rashes, fever, taste disturbances, proteinuria and neutropenia) are dose dependent.(ABSTRACT TRUNCATED AT 400 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

The influence of selective and nonselective prostaglandin inhibition on renin.

The finding that sulindac, in contrast to indomethacin, does not inhibit renal prostaglandins (PGs) can offer the means to study the role of systemic and/or renal PGs in the control of renin. Therefore we studied, using a randomized cross-over design, the influence of treatment with sulindac and indomethacin on plasma renin activity (PRA) of essential hypertensive patients, which was measured either after standing or after chronic captopril and chlorthalidone administration. In the captopril-treated group, serum thromboxane B2 (TXB2) and urinary 6-keto-PGF1alpha were significantly reduced by indomethacin, while sulindac reduced only serum TXB2. PRA was significantly reduced by indomethacin in the three groups and by sulindac only in standing and captopril-treated patients. These findings suggest that systemic PGs are mainly involved in the control of renin during standing and angiotensin-converting enzyme (ACE) inhibition, while mainly renal PGs play a role in the control of renin during chronic thiazide-like diuretic administration.

Adult↗
PubMed1984

Primary aldosteronism due to adrenal carcinomas.

In the present study two patients with aldosterone-producing adrenal carcinomas are reported. The clinical features were characterized by hypertension and severe hypokalemia with muscular weakness, flaccid paralysis of arms and legs, diarrhea and polyuria. In both cases excessively high plasma aldosterone levels and suppressed plasma renin activity were found. In contrast to most other cases with aldosterone-secreting tumours plasma cortisol, urinary free cortisol excretion, 17-hydroxy- and 17-ketosteroids were in the normal range. There was no clinical evidence of oversecretion of sex hormones. After adrenalectomy blood pressure and serum potassium normalized and the clinical symptoms disappeared. Plasma aldosterone and urinary aldosterone secretion returned to normal, while plasma renin activity remained low. Three and a half and 6 months later primary aldosteronism and the associated clinical symptoms reappeared due to hormonally active metastases. After introducing the antitumour drug o,p'-DDD in patient 1 aldosterone secretion normalized and the clinical status of the patient markedly improved. However, 10 months after diagnosis the patient died due to a haemorrhage from a liver metastasis. In patient 2 tumour-invaded regional lymph nodes were surgically removed with only minor changes in the hormone pattern.

Adrenal Cortex Neoplasms↗
PubMed1984

Clinical and systemic hemodynamic effects of nitrendipine.

The antihypertensive effects of nitrendipine were evaluated in 12 subjects with hypertension, one of whom could not tolerate the drug for more than 3 days; hence hemodynamics were studied in the 11 subjects who were treated for 2 wk. In one patient taking 40 mg twice a day, blood pressure reduction was associated with a hemodynamic pattern of hyperkinetic circulation. Of the other 10 subjects, all of whom were taking 20 mg twice a day, two did not respond, but 8 had significant reduction in mean arterial pressure (136 +/- 4.3 to 106 +/- 3.2 mm Hg) resulting from a decrease in total peripheral resistance (52 +/- 3.7 to 35 +/- 2.6 U X m2). Changes in cardiac output, heart rate, and cardiopulmonary volume varied widely among subjects, such that average changes did not attain significance. Heart rate and cardiopulmonary volume, however, changed in the same direction, which suggests that the alterations in both were related to the degree of reflex sympathetic stimulation induced by nitrendipine. Plasma renin activity (PRA) increased during treatment (2.6 +/- 1.0 to 9.3 +/- 4.1 ng/ml/hr), whereas the increase in plasma aldosterone (PA) levels did not attain significance (13.7 +/- 1.6 to 21.5 +/- 4.5 ng/dl). As a result, PA/PRA decreased (16.1 +/- 4.9 to 9.4 +/- 2.6). These results suggest that calcium entry blockade might have interfered with steroidogenesis, thus blunting the effect of increased PRA. Finally, blood pressure response to nitrendipine in the whole group correlated inversely with pretreatment PRA (r = -0.88), suggesting greater activity of the drug in low-renin hypertension.

Adult↗
PubMed1984

The influence of indomethacin and sulindac on some pharmacological actions of atenolol in hypertensive patients.

Indomethacin and sulindac were used as tools to study the role of renal and/or systemic prostaglandins in the pharmacological response to atenolol. Patients receiving chronic treatment with atenolol 100 mg received indomethacin 50 mg twice daily or sulindac 200 mg twice daily in a randomised crossover trial. Indomethacin significantly reduced the antihypertensive action of atenolol while sulindac had no effect. The role that systemic and/or renal prostaglandins may play in the antihypertensive action of atenolol is discussed with reference to renal PGI2 production and inhibition of platelet cyclo-oxygenase.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Interference of calcium entry blockade in vivo with pressor responses to alpha-adrenergic stimulation: effects of two unrelated blockers on responses to both exogenous and endogenously released norepinephrine.

To the extent that calcium availability is the final common mediator of vasoconstrictor responses, calcium entry blockade might interfere with physiologic responses to adrenergic stimulation. To test this hypothesis, we studied the effects of calcium entry blockade on pressor responses to norepinephrine in pithed, normal Sprague-Dawley rats in two different ways: (1) by evaluating the effects on pressor responsiveness to exogenous norepinephrine during differential blockade of alpha 1-(prazosin, 0.3 mg/kg) and of alpha 2-receptors (yohimbine, 0.3 mg/kg) and (2) by comparing the effects of calcium entry blockade with those of prazosin and those of rauwolscine (a specific alpha 2-antagonist) on pressor responses to infusions of both endogenously released norepinephrine (electrical stimulation of the pithing rod) and exogenous norepinephrine. In the presence of alpha 1-blockade, both nitrendipine (0.01 mg/kg) and verapamil (0.6 mg/kg) shifted the norepinephrine pressor dose-response curve to the right but were ineffective in alpha 2-blocked animals. Furthermore, nitrendipine (range 0.01 to 0.3 mg/kg) proved to be more effective (p less than .001) against exogenous norepinephrine than against electrical stimulation of the spinal cord, a behavior opposite that of selective alpha 1-blockade (prazosin) and directionally comparable to that of selective alpha 2-antagonism (rauwolscine). These data indicate that calcium entry blockade in vivo preferentially antagonizes the alpha 2-pressor component of exogenous norepinephrine. In addition, both calcium entry blockers were consistently more active (p less than .01) than rauwolscine (0.01 to 1 mg/kg) in antagonizing the pressor response to neural stimulation, suggesting that mechanisms different from "classical" alpha 2-antagonism may also contribute to the overall effect of calcium entry blockade on the adrenergic control of peripheral vascular tone.

Adrenergic alpha-Agonists↗