Altered myogenic constriction and endothelium-derived hyperpolarizing factor-mediated relaxation in small mesenteric arteries of hypertensive subtotally nephrectomized rats.
OBJECTIVE
Chronic renal failure (CRF) is associated with altered systemic arterial tone and hypertension. Myogenic constriction and endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation represent major vasoregulatory mechanisms in small systemic arteries. Elevated myogenic response and impaired EDHF might participate in the development of essential hypertension; however, their role in CRF-related hypertension is unknown. We investigated whether myogenic response and EDHF are altered in subtotally nephrectomized (sNX) rats and whether these changes are modifiable by chronic treatment with angiotensin-converting enzyme (ACE) inhibitor.


METHODS
In a pressure arteriograph, myogenic constriction and EDHF-mediated relaxation were evaluated in small mesenteric arteries isolated from male Wistar rats 15 weeks after either sham operation (n = 7) (SHAM), sNX (n = 12) or sNX followed by 9 weeks of treatment with lisinopril (sNX + LIS, 2.5 mg/kg, n = 13).


RESULTS
Surprisingly, myogenic response was reduced in hypertensive CRF rats (maximal myogenic tone: 37 +/- 2 and 18 +/- 4%, P < 0.01; peak myogenic index: -0.80 +/- 0.08 and -0.40 +/- 0.12%/mmHg, P < 0.05 in SHAM and sNX respectively). At the same time EDHF-mediated relaxation was also impaired (maximal response: 92 +/- 2 and 77 +/- 5%, P < 0.01; pD2: 6.5 +/- 0.1 and 5.9 +/- 0.1, P < 0.05). Both myogenic response and EDHF were inversely related to the severity of renal failure and restored by treatment with lisinopril to levels found in SHAM animals.


CONCLUSIONS
Major constrictive (myogenic) and dilatory (EDHF) mechanisms of small systemic arteries are impaired in hypertensive CRF rats. These alterations do not seem to participate in the development of hypertension, being rather directly related to the severity of renal impairment. Both systemic vascular changes might be restored by renoprotective treatment with ACE inhibitor.
Vettoretti
Simone
S
Department of Clinical Pharmacology, University Medical Center Groningen and Groningen Institute for Drug Exploration (GUIDE), University of Groningen, The Netherlands.
Ochodnicky
Peter
P
Buikema
Hendrik
H
Henning
Rob H
RH
Kluppel
C Alex
CA
de Zeeuw
Dick
D
van Dokkum
Richard P E
RP
D000792:Angiography; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D017706:Lisinopril / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D023421:Models, Animal; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology*; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001685:Biological Factors; C067410:endothelium-dependent hyperpolarization factor; D017706:Lisinopril