Relationship of alpha receptor types to hypotension and renal vasodilation caused by alpha blockers in conscious dogs.

Abstract

SUMMARY In conscious instrumented normotensive and two-kidney, one clip Goldblatt hypertensive dogs, we compared the effects of the a-receptor blocking agent, urapidil, on blood pressure, renal vascular resistance, heart rate,'and plasma renin activity with those of prazosin and phentolamine. Urapidil (2 mg/kg) and prazosin (0.25 mg/kg) decreased blood pressure and renal vascular resistance in both groups of animals, and urapidil caused a small increase in renal blood flow. Heart rate, but not plasma renin activity, was increased at the peak of the hypotension. Phentolamine had no significant effect on any of these parameters. All three agents markedly inhibited the renal vasoconstrictor responses to intraarterially administered phenylephrine and norepinephrine, and thus exhibited an (*|-receptor blocking action. Only urapidil significantly antagonized the response to B-HT 933, a selective os-receptor agonist, indicating that it also interacts at a 2 -receptor sites. Since both normotensive and hypertensive animals exhibited similar hypotensive responses after both urapidil and prazosin, the degree of a-receptor blockade achieved did not reveal greater sympathetic tone in renal hypertension. VIDENCE suggests that a,-receptors are concentrated at the adrenergic neuroeffector junction, and therefore deblocking agents are particularly effective in inhibiting sympathetic vascular tone.1 Adrenergic blocking agents such as prazosin act selectively on a,-receptors, inhibiting almost completely the vasoconstrictor action of the a,-agonist phenylephrine.2 Agents such as phentolamine, which block both a,-and a,-receptors, have complex effects since they can inhibit sympathetic vascular tone postjunctionally, but also enhance adrenergic transmitter release through blockade of a,-mediated negative feedback.1 Urapidil, a phenyl piperazine derivative, 4 possesses alpha,-blocking properties and may also stimulate a 2 -receptors in the central nervous system.' Thus, this agent has the potential capacity to inhibit sympathetic vascular tone at central and peripheral sites. The main purpose of the present investigation was to examine the effects of urapidil on blood pressure and renal hemodynamics in conscious instrumented normotensive and two-kidney, one clip Goldblatt hypertensive dogs and to ascertain the renal a-adrenergic receptor upon which it acts. MethodsTwelve dogs of either sex weighing 16-30 kg were used in this investigation. Throughout the study, dogs were fed puppy chow, which provided 67 mEq of sodium chloride daily. While anesthetized with pentobarbital, the dogs underwent two separate operations for implantation of femoral arterial and venous catheters, and approximately 1-2 weeks later for placement of a Zepeda blood flow probe (4-5 mm in diameter) around the left renal artery and a PE 10 catheter in the artery. Details of this technique have been published elsewhere. 6 The flow probe was located on the artery as close to the aorta as possible, and the catheter inserted retrograde into the artery at the site of...

Interaction with Histamine H₁-Receptors and Bronchospasmolytic Effects of Urapidil

“…It reduces arterial peripheral re 1 A preliminary presentation of these data was given at the 25th Spring Meeting of the Deutsche Pharmakologische Gesellschaft , sistance mainly via blockade of vascular a-adrenoceptors [Schoetensack et al, 1977a;Bousquet et al, 1983;Zimmerman and Largent, 1983;Eltze, 1984] accompan ied by a centrally mediated reduction of peripheral sympathetic tone [Schoeten sack et al, 1983;Sanders and Jurna 1985] and a weak /^-blockade [Freissmuth et al, 1984;Verberne and Rand, 1985;van Zwieten et al, 1985 a]. A further receptor-mediated effect of urapi dil is its moderate H¡-antihistaminic prop erty which probably does not contribute to its antihypertensive action [van Zwieten et al, 1985b).…”

Influence of Urapidil on Α‐ and Β‐adrenoreceptors in Pithed Rats

“…While the inhibition of stimulation-induced increase in heart rate has been taken in favour of an agonistic effect of urapidil at presynaptic a2adrenoreceptors, the results are not conclusive since nc further characterization by use of selective a2-adrenoreceptor antagonists has been attempted. Inhibition by urapidil of the renal vasoconstrictor response to the a2adrenoreceptor agonist azepexole has been observed in conscious dogs (Zimmerman & Largent, 1983). Thus, antagonism by urapidil of a2-&ciloreceptor-rnediated responses obscrved in vitro is also demonstrable in in vivo experiments.…”