Regional hemodynamic effects of rilmenidine and clonidine in the conscious spontaneously hypertensive rat.
Rilmenidine is an oxazoline analogue that has antihypertensive properties that resemble those of clonidine. Since rilmenidine has recently been described to have a relatively greater affinity for imidazoline receptors than clonidine, it was of interest to study whether this has functional consequences with regard to the regional hemodynamic responses. We investigated regional hemodynamics in conscious spontaneously hypertensive rats, equipped with miniature Doppler flow probes on the renal and mesenteric arteries and on the abdominal aorta. Clonidine (3-30 micrograms/kg) and rilmenidine (0.2-3 mg/kg) induced similar, dose-dependent reductions in heart rate. Both also induced an early hypertensive response, which was greater with rilmenidine, and similar later blood pressure reductions, which were maintained over 3 h. The early hypertensive response was associated with generalized vasoconstriction. Rilmenidine caused slightly greater mesenteric and hindquarter constriction than clonidine, whereas renal effects did not differ significantly. During the hypotensive phase, rilmenidine was a less potent mesenteric and hindquarter vasodilator than clonidine. During this phase, renal blood flow was at control levels, probably indicating autoregulation of renal flow. The minor differences in regional hemodynamic effects suggest that clonidine and rilmenidine can both be used as potent antihypertensives. The fact that rilmenidine has been suggested to possess less sedative side-effects suggests that, on this basis, it may be superior for antihypertensive drug therapy.
Smits
J F
JF
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Struyker-Boudier
H A
HA
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects; D000077769:Rilmenidine; D013152:Splanchnic Circulation / Q000187:drug effects
D000959:Antihypertensive Agents; D010080:Oxazoles; D003000:Clonidine; D000077769:Rilmenidine