Perindopril treatment affects both preglomerular renal vascular lumen dimensions and in vivo responsiveness to vasoconstrictors in spontaneously hypertensive rats.
We have previously shown that chronic treatment with angiotensin-converting enzyme inhibition (ACEI) did not reverse hypertrophy of the renal arterial wall in spontaneously hypertensive rats (SHR). In this study we determined the effects of perindopril on the functional properties of the renal vasculature in vivo and on its resistance to flow at maximal dilatation in vitro, a measure of vessel lumen diameter. Two groups of SHR were studied: untreated or treated with perindopril (3 mg/kg per day) in their drinking water from 4 weeks of age. At 10 weeks, (1) vessel lumen characteristics were assessed using a maximally dilated in vitro isolated kidney perfusion and (2) the renal vasoconstrictor responses to bolus doses of vasoactive agents (angiotensin II and phenylephrine) 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-glomerular 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 controls (P<.001). In vivo, renal vasoconstrictor responses to increasing doses of both vasoconstrictor agents were significantly less marked in the perindopril-treated SHR than in untreated SHR (P<.05). Thus, chronic ACEI increased average renal vessel lumen diameter in SHR, predominantly in preglomerular vessels, and reduced renal vasoconstrictor responsiveness in vivo, findings compatible with remodeling of the preglomerular vasculature around a greater lumen.
Bergström
G
G
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Johansson
I
I
Stevenson
K M
KM
Kett
M M
MM
Anderson
W P
WP
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D007211:Indoles / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D020913:Perindopril; D051381:Rats; D011918:Rats, Inbred SHR; D012077:Renal Artery / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D014662:Vasoconstrictor Agents; D020913:Perindopril