Attenuated afferent arteriolar response to acetylcholine in Goldblatt hypertension.

Abstract

We tested the hypothesis that endothelium-dependent afferent arteriolar vasodilation is impaired in the nonclipped kidney of two-kidney, one clip Goldblatt hypertensive rats relative to sham-operated controls. Five to six weeks after positioning of a 0.25-mm clip on the left renal artery, systolic pressure averaged 173±10 mm Hg in Goldblatt rats and 118±4 mm Hg in controls (p<0.01). The right kidney was harvested for videometric study of the microvasculature using the in vitro blood-perfused juxtamedullary nephron technique. Kidneys from Goldblatt and control rats were perfused at renal arterial pressures of 150 and 110 mm Hg, respectively. Afferent arteriolar inside diameter did not differ between control (20.3±0.7 fim) and Goldblatt (21.1±1.7 fim) kidneys. Determination of afferent responses to increasing concentrations of the endothelium-dependent vasodilator acetylcholine (1 nM to 10 fiM) in the bathing solution unveiled a shift to the right in the dose-response relation in Goldblatt rats. Afferent arterioles from control kidneys dilated significantly when exposed to 1 nM acetylcholine, whereas a 1,000-fold higher concentration was required to dilate arterioles from Goldblatt rats. Sodium nitroprusside, an endothelium-independent vasodilator, increased afferent diameter to a similar extent in both groups. In a separate group of normal kidneys, vasodilator responses to 10 /iM acetylcholine were completely blocked by 1,000 /tM nitro-L-arginine, an inhibitor of nitric oxide synthesis. Thus, endothelium-dependent afferent vasodilation appears to be impaired in the nonclipped kidney of Goldblatt hypertensive rats. This phenomenon could contribute to the altered renal hemodynamic status characteristic of Goldblatt hypertension. (Hypertension 1992;19:785-789) KEY WORDS • microcirculation • vasodilation • acetylcholine • Goldblatt hypertension • nitroprusside I n recent years, increasing attention has focused on the role of the endothelium as a determinant of vascular function under physiological and pathophysiological conditions. In this regard, the development or maintenance of hypertension has been suggested to involve an inappropriately reduced endothelium-dependent dilator influence on the vasculature.12 Indeed, arterial rings and strips harvested from hypertensive animals exhibit markedly attenuated responses to endothelium-dependent vasodilators. "6 Despite the growing body of evidence implicating impaired endothelium-dependent vasodilation in hypertension, little information is available regarding the involvement or integrity of this system in the renal macrovascular and microvascular dysfunction characteristic of most models of hypertension. The two-kidney, one clip (2K1C) model of renovascular hypertension requires involvement of the renin-angiotensin system for development of the hypertension 7 ; however, alterations in vascular structure and neurohumoral influences have also been implicated. "10 Thus, the cause of the sustained systemic and renal hemodynamic dysfunction in 2K1C hypertension remains unc...

Increase in Functional Ca 2+ Channels in Cerebral Smooth Muscle With Renal Hypertension

“…For example, an increase in channel availability with hypertension could be due to impaired endothelial function, as has been documented in SHR, 2K1C, and other models of hypertension. [37][38][39][40][41][42] In the basilar artery, hypertension-induced endothelial dysfunction would result in loss of NO and, thus, larger Ca 2ϩ currents, because NO decreases the availability of Ca 2ϩ channels via a cGMP-mediated mechanism that does not alter channel properties. 27 In our preparation, we cannot exclude the possibility that channel expression was increased along with a concomitant increase in channel insertion into the cell membrane.…”