Acute systemic and regional haemodynamic profile of prazosin in conscious hypertensive rabbits

Bolt, Gert; Saxena, Pramod R.

doi:10.1016/0014-2999(84)90382-0

Cited by 7 publications

(6 citation statements)

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“…In the present study, renal blood flow was not measured. Previous studies in conscious rabbits have demonstrated that acute injections of prazosin, which decrease blood pressure to an extent similar to or greater than that in the present study, did not alter renal blood flow (Bolt & Saxena, 1984). Clinical studies have shown the absence of changes in renal blood flow despite a significant decrease in blood pressure (Bauer et al, 1984).…”

Section: Discussionsupporting

confidence: 67%

Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats

Penner

Smyth

1988

British J Pharmacology

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The effect of chronic prazosin pretreatment (3 days) on the ability to excrete a modest saline load (i.v. saline, 0.097 ml min−1) was studied in the anaesthetized rat. Three days before the experiment, the drinking water was replaced with 0.5% dextrose (control), 0.015 mg ml−1 prazosin in 0.5% dextrose (low dose) or 0.15 mg ml−1 prazosin in 0.5% dextrose (high dose). The selectivity of the prazosin for α1‐adrenoceptors was evaluated in pithed rats. The pressor response to phenylephrine was partially attenuated by the low dose of prazosin and completely attenuated by the high dose of prazosin. The pressor response to clonidine was slightly decreased by the 3 day prazosin pretreatment indicating a selectivity for α1‐adrenoceptors. In rats pretreated with the low dose of prazosin, there was a significant decrease in sodium and water, but not potassium excretion as compared to the control group. Captopril failed to alter these effects of the low dose of prazosin. Blood pressure and creatinine clearance were the same in both groups. In rats pretreated with the high dose of prazosin, there was a further decrease in sodium and water but not potassium excretion. However, this dose of prazosin also significantly decreased blood pressure and increased creatinine clearance. A decrease in renal perfusion pressure with an aortic clamp to the same level as that observed with the high prazosin dose also decreased sodium and water but not potassium excretion. The decrease in sodium and water excretion was not as great as that observed with the high dose of prazosin. The results indicate that chronic α1‐adrenoceptor blockade with prazosin attenuates the ability to excrete a saline load in a dose‐related manner. Whether this inability to excrete a saline load is analogous to the sodium and water retention observed with the clinical use of prazosin remains to be determined.

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Section: Discussionsupporting

confidence: 67%

Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats

Penner

Smyth

1988

British J Pharmacology

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“…The absence of reflex tachycardia during the prolonged hypotensive action of ketanserin may be related to the reported interference of the drug with the autonomic nervous system activity, 5 l0 where it causes a decrease in sympathetic outflow." Remarkably, a similar heart rate response has been observed with hypotensive doses of the a,-selective adrenergic receptor antagonist prazosin in conscious normotensive 23 and hypertensive 12 rabbits. Pronounced tachycardia was only observed during the first few minutes after the acute administration of prazosin despite sustained hypotension.…”

Section: Discussion Cardiovascular Profile Of Ketanserinmentioning

confidence: 49%

“…7 -31 In contrast to prazosin, ketanserin moderately increased the cardiac output in the present study. It may be that the direct vasodilator action of ketanserin, which is not observed with prazosin, 12 contributed to the relatively more pronounced cardiac stimulation during the prolonged hypotensive phase of ketanserin. On the other hand, both the less pronounced increase in cardiac output after ketanserin, 1.0 mg/kg, and the decrease in this variable after prazosin, 0.1 mg/kg, can be explained by a reduction in venous return secondary to dilatation of venous capacitance vessels, 712 -32 which becomes more prominent when higher doses of the drugs are used.…”

Section: A-adrenergic Receptor Blockadementioning

confidence: 97%

“…4 0 ± 0.01; P ,^, 33 ± 1,32 ± 1,31 ± 1, and 30 ± 1 mm Hg; and P^, 94 ± 3,93 ± 3,95 ± 3, and 95 ± 4 mm Hg. In a previous study we 12 measured the effects of prazosin (0.01, 0.03, and 0.10 mg/kg i.v.) in conscious hypertensive rabbits using the same experimental protocol, except that the microspheres were injected 15 minutes after the subsequent doses of prazosin when stable heart rate and blood pressure responses were measured.…”

Section: Systemic and Regional Hemodynamicsmentioning

confidence: 99%

“…In addition, we determined the changes in regional blood flows and resistances after ketanserin administration to characterize the complete hemodynamic profile of this new antihypertensive drug. As we recently have studied the effects of the a,-selective adrenergic receptor antagonist prazosin using the same methodology, 12 we were able to compare the complete hemodynamic profiles of the two compounds in conscious hypertensive rabbits. A preliminary report of this study was presented at a meeting of the British Pharmacological Society.…”

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confidence: 99%

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Cardiovascular profile and hypotensive mechanism of ketanserin in the rabbit.

Bolt¹,

Saxena²

1985

Hypertension

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SUMMARY Using the radioactive microsphere technique, we studied the systemic and regional hemodynamic effects of ketanserin in conscious renal hypertensive rabbits. To characterize the hypotensive mechanism of the compound, we evaluated its antagonism toward 5-hydroxytryptamine 2 and a,-adrenergic receptors at hypotensive doses and compared the cardiovascular profile of ketanserin with that of the a,-selective adrenergic receptor antagonist prazosin. Ketanserin (0.1, 0.3, and 1.0 mg/kg i.v.) produced a biphasic effect on the arterial blood pressure. A short, pronounced fall in blood pressure accompanied by tachycardia preceded a more moderate and longer lasting doserelated hypotensive effect. The presence of adequate autonomic nervous system activity seems to be required for the prolonged hypotensive action of ketanserin because, in animals pretreated with hexamethonium (30 mg/kg), the blood pressure, after an initial decrease, returned to baseline values within a few minutes after each ketanserin dose. Ketanserin inhibited the pressor responses produced by 5-hydroxytryptamine (10, 30, and 100 /zg/kg i.v.) and phenylephrine (3, 10, and 30 Mg/kg '• v -)> which indicates that, at hypotensive doses, the compound antagonized both 5-hydroxytryptamine 2 receptors and aj-adrenergic receptors. At doses that caused a comparable degree of a,-adrenergic receptor blockade, ketanserin (0.1, 0.3, and 1.0 mg/kg i.v.) as well as prazosin (0.01, 0.03, and 0.10 mg/kg i.v.) decreased the blood pressure as a result of a reduction in total peripheral resistance. While cardiac output increased, especially at the lower doses of ketanserin, a moderate decrease in this variable contributed to the hypotensive effect of the highest dose of prazosin. Both compounds decreased the vascular resistance in the kidneys, gastrointestinal tract, and bones, whereas that in the skin and skeletal muscles was not significantly altered. In contrast to prazosin, ketanserin also caused vasodilatation in the coronary and cerebral vascular beds. The results suggest that, in addition to a direct vasodilator effect of short duration, ketanserin has a prolonged hypotensive action in conscious hypertensive rabbits that is predominantly due to ai-adrenergic receptor blockade. has been shown to reduce the blood pressure in animals 43 and humans 6 -7 by a mechanism that is still a matter of debate. In hypertensive patients ketanserin can lower the arterial blood pressure without causing any attenuation of the pressor response to phenylephrine. 7 This pharmacological evidence has been used to support the concept that a blockade of 5-HT 2 receptors is responsible for the antihypertensive effect of the drug.7 ' 8 In contrast, studies in spontaneously hypertensive rats provide arguments that ketanserin lowers the blood pressure merely by a competitive blockade of a,-adrenergic receptors. 4 -5 -9 Moreover, a central action has been suggested to contribute to the hypotensive action of ketanserin. 10-" To provide further information on the hypotensive mechanism of ketan...

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The differential effects of prazosin and hydralazine on sympathoadrenal activity in conscious rats

1989

European Journal of Pharmacology

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Acute systemic and regional haemodynamic profile of prazosin in conscious hypertensive rabbits

Cited by 7 publications

References 20 publications

Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats

Chronic prazosin attenuates the natriuretic response to a modest saline load in anaesthetized rats

Cardiovascular profile and hypotensive mechanism of ketanserin in the rabbit.

The differential effects of prazosin and hydralazine on sympathoadrenal activity in conscious rats

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