Perindopril changes the mesenteric pressure profile of conscious hypertensive and normotensive rats.

Abstract

Information about how antihypertensive therapy affects the arterial blood pressure profile in conscious animals is at present not available. Here we report measurements of part of the pressure profile in conscious spontaneously hypertensive rats (SHR, n=7) and Wistar-Kyoto (WKY, n=7) rats before and after treatment with the angiotensin-converting enzyme inhibitor perindopril. The previously developed technique that we used, provided simultaneous measurements of the undisturbed arterial blood pressure at the base of mesenteric arcades ( P^ diameter, approximately 100 nm) and systemic mean blood pressure (MBP). The ratio P <rc /MBP was 63±2% (mean±SEM) in SHR and 64±3% in WKY rats. When a bolus of perindopril (0.8 mg/kg) was injected into the aorta, P^/MBP fell within 2 minutes to 51±2% (P<.05) for SHR and 56±2% (P< .05) for WKY rats, and these levels were maintained for the next hour. In contrast, MBP did not change for approximately 5A lthough the action of antihypertensive drugs on / \ systemic pressure (eg, mean blood pressure A. \ . [MBP]) is widely studied, there is little evidence concerning the action of such drugs on the profile of the blood pressure through the vascular system. Current techniques do not allow such measurements to be made in humans, and in animal studies investigations have been prevented because the experimental procedures used could be made only in anesthetized animals. A notable exception is the study of Wiederhelm and Weston, 1 who measured microvascular pressures in the wings of restrained bats, but the effects of drugs were not investigated. Because anesthesia and surgery can seriously affect the pressure profile, 2 we have recently developed a technique that allows measurement of the undisturbed intra-arterial pressure at the base of the mesenteric arcade (P^) in conscious rats.3 These arteries have a diameter of approximately 100 /*m (N. Korsgaard, personal communication). The results showed that in Wistar rats approximately one third of the resistance of the mesenteric bed lay in macroarteries, ie, arteries proximal to the base of the mesenteric arcades. This has suggested that the peripheral resistance is located not only in the more distal microarteries but that a significant portion resides in the macroarteries, as indeed has been suggested in experiments made Received August 5, 1993; accepted in revised form November 3, 1993.From the Institute of Pharmacology, University of Aarhus (Denmark).Correspondence to Dr Kent Lodberg Christensen, c/o Prof M.J. Mulvany, Institute of Pharmacology, University of Aarhus, Universitetsparken 240, 8000 Aarhus C, Denmark. minutes in either strain, whereas after 1 hour MBP still had not changed significantly in WKY rats, but MBP had fallen by 16±2% (P<.05) in SHR. The experiments suggest that in the mesentery (1) the elevated resistance in the arterial system in SHR is present in both macroarteries (ie, vessels proximal to the base of the arcades) and in the more distal microarteries and veins, (2) for at least 1 hour perindopril cause...

Location of Resistance Arteries

“…Our own opinion is that the fractional blood pressure drop to vessels of a certain size is about equal in normo- and hypertensive animals, suggesting that resistance artery abnormalities are widespread rather than localized to a certain part of the resistance vasculature. This is what we have observed in SHR in the conscious state in the intestinal circulation [32]. Given the discussion above, much of the heterogeneity may be ascribed to the different anesthetics and preparation procedures used.…”

“…DeLano et al [18]observed the same in three different skeletal muscles in anesthetized 12- to 16-week-old SHR, as did Bohlen [30]in the brain of 4- to 5-week-old SHR and Roy and Mayrovitz [31]in the cremaster muscle of SHR. This has also been our experience in conscious SHR [32]. In contrast to these findings of normal blood pressure profile in hypertension, other investigators have reported that specific parts of the resistance vasculature are responsible for the increased resistance of SHR.…”

Alterations in flow-dependent vasomotor tone in spontaneously hypertensive rats.

“…22 -25 Furthermore, it has been suggested that the macroarteries contribute to the increased peripheral resistance observed in anesthetized hypertensive rats. 22 - 24 Christensen and Murvany 26 recently reported that in normotensive and unanesthetized SHR, approximately one third of the resistance of the mesenteric bed lies in macroarteries. In addition, the perfusion pressure recorded in the larger mesenteric arteries reflects the resistance of the overall mesenteric bed (macroarteries and microarteries) calculated as the pressure-flow ratio.…”

Arterial Structural Changes in Hypertension: A Consideration of Methodology, Terminology and Functional Consequence

“…It can also be argued that the ideal pressure would be that prevailing in vivo in the conscious animal, but in this regard, the in vivo pressure is not always known. However, it has been shown that the mean arterial pressure at the base of the mesenteric arcade of rats is approximately 60% of aortic mean arterial pressure in SHR and normotensive controls [24, 25]. Based upon the latter of these two studies, estimations of the pressures at this site in approximately 20-week-old SHR and WKY rats were reported to be 105 and 74 mmHg, respectively, by Bund [26], and 103 and 72 mm Hg, respectively, by Izzard et al [27].…”