High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries

Abstract

. High-salt diet impairs vascular relaxation mechanisms in rat middle cerebral arteries. Am J Physiol Heart Circ Physiol 284: H1124-H1133, 2003. First published November 27, 2002 10.1152/ajpheart.00835. 2002-Male Sprague-Dawley rats were maintained on a low-salt (LS) diet (0.4% NaCl) or a high-salt (HS) diet (4% NaCl) for 3 days or 4 wk. PO2 reduction to 40-45 mmHg, the stable prostacyclin analog iloprost (10 pg/ml), and stimulatory G protein activation with cholera toxin (1 ng/ml) caused vascular smooth muscle (VSM) hyperpolarization, increased cAMP production, and dilation in cerebral arteries from rats on a LS diet. Arteries from rats on a HS diet exhibited VSM depolarization and constriction in response to hypoxia and iloprost, failed to dilate or hyperpolarize in response to cholera toxin, and cAMP production did not increase in response to hypoxia, iloprost, or cholera toxin. Low-dose angiotensin II infusion (5 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 iv) restored normal responses to reduced PO2 and iloprost in arteries from animals on a HS diet. These observations suggest that angiotensin II suppression with a HS diet leads to impaired relaxation of cerebral arteries in response to vasodilator stimuli acting at the cell membrane. salt intake; hypertension; angiotensin; hypoxia; vascular smooth muscle; endothelium PREVIOUS STUDIES (8,11,19) have demonstrated that both chronic (4-8 wk) volume expanded hypertension caused by reduced renal mass (RRM) with exposure to a high-salt diet and chronic exposure of normotensive rats to a high-salt diet lead to structural changes in arterioles, reductions in microvessel density, and an impaired relaxation of skeletal muscle resistance vessels in response to a variety of vasodilator stimuli, including reduced PO 2 , the stable prostacyclin analog iloprost, and acetylcholine. Subsequent studies demonstrated that alterations in microvessel structure, density, and reactivity in normotensive animals and RRM hypertensive rats on a high-salt diet develop quite rapidly. For example, Hansen-Smith et al. (15) demonstrated that microvascular rarefaction and profound ultrastructural alterations occur in arterioles of RRM hypertensive rats and normotensive animals after only 3 days on a high-salt diet. Other studies (10)(11)(12)38) have demonstrated that vasodilator responses to reduced PO 2 , acetylcholine, and iloprost are also impaired after short-term exposure to high-salt diet. The microvascular rarefaction and the reduced relaxation of resistance arteries to vasodilator stimuli in animals on a high-salt diet may be related to the angiotensin II (ANG II) suppression that occurs in response to elevated dietary salt intake because both the reduction of cremasteric microvessel density (16) and the impaired dilation of skeletal muscle resistance arteries in response to acetylcholine, iloprost, and reduced PO 2 in animals on a high-salt diet can be prevented by infusion of a low dose of ANG II (37,38).To date, the majority of studies investigating changes in vascular control mechanisms with a highsa...

Introgression of chromosome 13 in Dahl salt-sensitive genetic background restores cerebral vascular relaxation

“…Given the demonstrated importance of ANG II in maintaining normal vascular relaxation mechanisms (15,38,39), it is possible that the intrinsic alterations in the relaxation of middle cerebral arteries from Dahl S rats on a low-salt diet are the result of the chronic low levels of ANG II in this strain of rats. This hypothesis is further supported by the finding that SS-13 BN and BN rats on a high-salt diet (which suppresses ANG II levels in response to elevated dietary salt intake) exhibit impaired vascular relaxation in response to ACh and hypoxia, as previously described for Sprague-Dawley rats (29,38,39). In Sprague-Dawley rats, the impaired response to ACh, hypoxia, and other vasodilator stimuli is the result of suppression of ANG II, since chronic intravenous infusion of a low dose of ANG II for 3 days restores normal vascular relaxation in response to these stimuli, despite the continued maintenance of the animals on the high-salt diet (38,39).…”

“…One may speculate that there is an imbalance between vasoconstrictor and vasodilator mediators that are released in response to ACh and hypoxia in arteries of Dahl S rats. Possible support for this speculation may be found in previous studies of SpragueDawley rats showing that a high-salt diet leads to an enhanced release of the vasoconstrictor mediator thromboxane A 2 during exposure to ACh and hypoxia (29). With this in mind, it is possible that chronically low ANG II levels in Dahl S rats on a low-salt diet are associated with the lack of an essential stimulus required to maintain normal function of vascular relaxation mechanisms that are important in mediating increases in blood flow in response to vasodilator stimuli.…”

High dietary salt reduces the contribution of 20-HETE to arteriolar oxygen responsiveness in skeletal muscle

“…This suggests that the reduced vasoconstriction to exogenous 20-HETE in salt-fed animals is due to a loss of that part of the response linked to reductions in K Ca channel activity. It seems unlikely that this is due to a general resistance of K Ca channels to inhibition, since previous studies have documented that K ϩ channel function and resting vascular smooth muscle membrane potential are not altered by high salt intake in normotensive rats (14,32), and, as stated above, we found no difference between dietary groups in the effects of TEA or IbTx on resting arteriolar tone. Instead, high salt intake may lead to the disruption of some 20-HETE-triggered event in vascular smooth muscle that precedes K Ca channel inhibition.…”

Restoration of normal vascular relaxation mechanisms in cerebral arteries by chromosomal substitution in consomic SS.13BNrats

“…For example, an impaired relaxation in response to vasodilator stimuli has been documented in many experimental animal models of hypertension (9 -11, 15, 32, 35, 39, 53) and in hypertensive humans (3, 13, 42-44, 49, 50). Other studies (31,32,34,48) have shown that high-salt diet alone leads to impaired vasodilation in arterioles and resistance arteries of Sprague-Dawley rats, in the absence of a change in blood pressure. Impairment of vascular relaxation in response to vasodilator stimuli during exposure to high-salt diet appears to be caused by the suppression of circulating levels of angiotensin II (ANG II) that occurs in response to elevated dietary salt intake (19,21).…”

“…For example, an impaired relaxation in response to vasodilator stimuli has been documented in many experimental animal models of hypertension (9 -11, 15, 32, 35, 39, 53) and in hypertensive humans (3, 13, 42-44, 49, 50). Other studies (31,32,34,48) have shown that high-salt diet alone leads to impaired vasodilation in arterioles and resistance arteries of Sprague-Dawley rats, in the absence of a change in blood pressure.…”