title: Effects of prolonged blockade of the renin angiotensin system on striated muscle microcirculation of spontaneously hypertensive rats.
abstract: Changes in microcirculation play an important role in the pathogenesis and maintenance of hypertension. The changes can be due to an alteration in vessel diameter or in the number of small blood vessels. In this study, the effects of prolonged administration of different blockers of the renin angiotensin system on the microcirculation of the cutaneous maximus muscle of young spontaneously hypertensive rats were determined by using the dorsal microcirculatory chamber model. Animals were treated with the angiotensin-converting enzyme inhibitor (ACE inhibitor) benazeprilat (3 mg/kg/d) or the specific angiotensin II AT1 receptor antagonist valsartan (3 mg/kg/d) for 4 weeks. Blood pressure was significantly lowered by 22 to 33% and to a similar extent in both treatment groups, whereas blood pressure in the control group continued to rise. Microvascular diameters and density were measured before and during the drug treatment and compared with those in the control group. There was no significant effect of either of the drug treatments on vascular diameters when compared with the control group for any vessel type (arterioles or venules). In contrast, there was a significant decrease in small arteriolar and venular density and in large venular density after treatment with the ACE inhibitor, whereas the angiotensin II AT1 receptor antagonist had no significant effect. The data do not suggest a role for angiotensin II in the long-term control of striated muscle microvascular tone. However, angiotensin II may be involved in microvascular growth via a non-AT1 receptor-mediated mechanism, or other vasoactive peptides degraded by ACE may contribute to the effects of the ACE inhibitor.
authors.affiliation: Department of Pharmacology, University of Limburg, Maastricht, Netherlands.
authors.forename: K J
authors.initials: KJ
authors.lastname: Scheidegger
authors.forename: J M
authors.initials: JM
authors.lastname: Wood
authors.forename: H
authors.initials: H
authors.lastname: van Essen
authors.forename: H A
authors.initials: HA
authors.lastname: Struijker-Boudier
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; C052133:benazeprilat