In vitro perfusion studies of resistance artery function in genetic hypertension.

Abstract

To examine the function of resistance-sized arteries in hypertension under in vitro conditions that approximate in Wvo conditions as much as possible, we mounted segments of second-order mesenteric resistance arteries from spontaneously hypertensive rats (SHR) and Wistar-Kyoto normotensive control rats aged 12 to 13 weeks in a perfusion myograph and exposed them to conditions of constant flow and pressure. The endothelial integrity was validated both functionally and histologically. Vascular sensitivity to norepinephrine was examined when the hormone was applied either intraluminally or extraluminally and before and after removal of the endothelium. Both endothelium-dependent and -independent dilatation was assessed by the intraluminal application of acetylcholine and sodium nitroprusside, respectively. Sodium nitroprusside was applied to arteries after endothelium removal. Arterial responses were measured by changes in intraluminal diameter recorded with a video camera and imaging system. Vessels from SHR demonstrated depressed endothelium-dependent relaxation but similar endotheliumindependent relaxation and greater sensitivity to norepinephrine with both intraluminal and extraluminal application. Removal of the endothelium abolished the differences in sensitivity to norepinephrine between the two strains. The results demonstrate that resistance arteries from SHR when examined under in vitro perfusion display enhanced sensitivity to norepinephrine due to depressed endotheliumdependent dilatation, and the data suggest that functional modifications in the endothelium may play an important role in hypertensive vascular disease. (Hypertension. 1993;22:486-495.) KEY WORDS • endothelium • norepinephrine • acetylcholine • nitroprusside • vascular resistance • hypertension, genetic • rats, inbred SHR

Pivotal Role of Renal Kallikrein-Kinin System in the Development of Hypertension and Approaches to New Drugs Based on This Relationship

“…Perfused segments of second order mesenteric resistance arteries from SHR show greater sensitivity to norepinephrine than those from WKY. This increase was due to depressed endothelium dependent dilatation, since removal of the endothelium abolished the difference in sensitivity to norepinephrine between the two strains (204). In humans, normotensive subjects with positive family histories of hypertension are characterized by a higher sensitivity to angiotensin II in the systemic and renal circulation than in subjects with negative family histories of hypertension (205).…”

Resistance Artery Mechanics, Structure, and Extracellular Components in Spontaneously Hypertensive Rats

“…10 A third-order artery (Ϸ2 mm) was placed on 2 glass microcannulas in a pressure myograph and adjusted so that vessel walls were parallel without stretch. 11 Vessels were equilibrated (1 hour) under constant intraluminal pressure (45 mm Hg) with warm (37°C) physiological salt solution (PSS), which was bubbled with 95% air and 5% CO 2 to achieve a pH of 7.4 to 7.45. Vessels were used if they constricted Ͼ50% in response to potassium (125 mmol/L KCl) with norepinephrine (10 Ϫ5 mol/L) and to norepinephrine alone (10 Ϫ5 mol/L).…”

Vascular Dilation Responses of Rat Small Mesenteric Arteries at High Intravascular Pressure in Spontaneously Hypertensive Rats

“…[16][17][18][19][20][21] However, such studies have a potential problem: dilation responses of small arteries from hypertensive subjects have been examined under normotensive pressure in order to provide experimental conditions identical to those for the normotensive control groups. Because it is plausible that the functional properties of resistance arteries may differ at high intravascular pressures because of in vivo adaptation, assessing the properties of hypertensive resistance arteries under normotensive conditions may provide accurate yet non-relevant information.…”

“…[16][17][18][19][20][21] However, those studies, which investigated the dilatation responses of small arteries to several agonists or flow by pressurized myography, were only performed under normotensive conditions, and the "normotensive" intraluminal pressures differed among them. Small mesenteric arteries (SMA) are usually exposed to pressures of 30 or 45 mmHg, [16][17][18] whereas small arteries obtained from skeletal muscle are exposed to greater pressures. 19 Pressurized small artery preparations also have been used in several human studies: subcutaneous small arteries obtained from hypertensive patients were exposed to 60 mmHg intraluminal pressure and endothelial function was assessed at this pressure state.…”