PERINDOPRIL TREATMENT AFFECTS BOTH PREGLOMERULAR RENAL VASCULAR LUMENDIMENSIONS AND IN-VIVO RESPONSIVENESS TO VASOCONSTRICTORS IN SPONTANEOUSLY HYPERTENSIVE RATS

We have previously shown that chronic treatment with angiotensin-conve rting enzyme inhibition (ACEI) did not reverse hypertrophy of the rena l arterial wall in spontaneously hypertensive rats (SHR). In this stud y we determined the effects of perindopril on the functional propertie s of the renal vasculature in vivo and on its resistance to flow at ma ximal dilatation in vitro, a measure of vessel lumen diameter. Two gro ups of SHR were studied: untreated or treated with perindopril (3 mg/k g per day) in their drinking water from 4 weeks of age. At 10 weeks, ( 1) vessel lumen characteristics were assessed using a maximally dilate d in vitro isolated kidney perfusion and (2) the renal vasoconstrictor responses to bolus doses of vasoactive agents (angiotensin II and phe nylephrine) administered into the renal artery were measured in vivo ( anesthetized rats). Mean arterial pressure was significantly lower in conscious SHR treated with perindopril (132+/-2 versus 97+/-2 mm Hg, P <.001). In vitro, the pressure-flow relationship and the pressure-glom erular filtration rate relationship were both shifted significantly to the left (P<.001). The perindopril treated kidneys began filtering at a significantly lower threshold perfusion pressure than nontreated co ntrols (P<.001). In vivo, renal vasoconstrictor responses to increasin g doses of both vasoconstrictor agents were significantly less marked in the perindopril-treated SHR than in untreated SHR (P<.05). Thus, ch ronic ACEI increased average renal vessel lumen diameter in SHR, predo minantly in preglomerular vessels, and reduced renal vasoconstrictor r esponsiveness in vivo, findings compatible with remodeling of the preg lomerular vasculature around a greater lumen.