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Age-dependent enhancement of vascular phospholipid (PL) deacylation-reacylation cycle in spontaneously hypertensive rats (SHRs)
EFFECT OF DIETARY SODIUM AND POTASSIUM CONTENT ON
WEDNESDAY, MARCH 18, 1981 PM hfYPERTENS/ON-RESEARCH 4:OQ-5:oo
SYMPATHETIC ACTIVITY IN spSHR. Albert Schdmig, MD, Rainer Diets, MD, Wolfgang, Rascher,MD Ruth Strasser, MD, and Wolfgang Kiibler, MD, Dept. of Cardiology University of Heidelberg, Germany.
AGE-DEPENDENT ENHANCEMENT OF VASCULAR PHOSPHOLIPID (PL) DRACYLATION-RRACYLATION CYCLE IN SPONTANEOUSLY HYPERTEN~IVE RATS (SHRS). Catherine Limas,MD and Constantinos J.Limas,MD;Veterans Administration Medical Center and the University of Minnesota, Minneapolis, Minnesota. Substrate availability is a key step in prostaglandin (PG) synthesis regulation and depends,to a large extent,on the activity of membrane phospholipase A2(PLase). We havecompared PG synthesis and Plase activity inaortas of SHRs and WKYs as a function of age.At 7 weeks,there is no difference in either PG or Plase between the two groups.With advancing age,aortic PG synthesis increases in both SHRs and WKYs but is significantly higher in hypertensive rats (0.52*0.04 nmol PGI2/mg/l5 min in SHRs at 42 wks compared to 0.29+0.04 nmol/mg/l5 min in WKYs,p
AN EXPERIMEN~L MODEL To ~EI+IDNsTRATROBJECTIVELY ME AsSOCIATION OF LABILE HYPERTENSION TU VASCULAR COMPLICATION &&d A. -M.D.; Robert Barndt, M.D., University of Southern Calftornls, Los Angeles, CA. The association between labile hypertension and vascular complications has been suspected epldemlologically. In the absence of an objective method of validation, we deslgned a prospective, randomiced study to investigate Ztrenty-four New Zealand rabbits this quantitatively. were randomlsed into three equal groups. One group of 8 Two other rabblts were used as age-matched controls. groups were fed a high (2%) cholesterol (Chol.) diet for One group of Chol. fed rabbits was given ran6 months. dom numbers of noreplnephrine (NOR) infusions (1 mg per 30 minutes) dally during the fourth month of Chol. feeding to induce labile hypertension. Significant elevatlon of blood pressure (BP) compared to baseline BP was obtained (mea-172, range-140-190mm Hg, P
478
February 1981
The American Journal of CARDIOLOGY
Dietary sodium loading in stroke prone spontaneously hyper tensive rats (spSHR) accelerates the rise in blood pressure whereas a potassium rich diet causes an attenuation of the development of hypertension. Since sympathetic activity and vascular reactivity to noradrenaline (NA) is elevated in spSHR as compared to WKR, we investigated the effects of changes in dietary sodium and potassium content on these parameters. The reactivity of vascular smooth muscle to NA was enhanced following dietary sodium loading as compared to normal fed animals and rats on a diet in which sodium was partially replaced by potassium (HSP diet : 650 mm01 N&l/kg and 200 mm01 KCl/kg). A high sodium diet (HS diet: 1000 mm01 N&l/kg) for a period of 14 days resulted in a rise of plasma NA concentration after cold exposition from 368 + 53 to 842 + 30 rig/l and of adrenaline (A) from 245 + 71to 1168 + 357 rig/l,,being markedly less pronounced in normal fed-spSHR NA from 244 + 30 to 448 + 51 ng/ml and A from 202 + 56 to 374 + 49 ns/l. 1n addition, a supersensitivity 07 vasculatur~ to NA was observed (ED50: 1.66 + 0.18 vs 2.4 + 0.26 nmol NA), which was the consequence of a reduced cocaine dependent uptake (uptake 1) of NA after a high sodium diet (70 + 3 vs 96 + 8 pmol/min/g tissue). Feeding with the potassium substituted diet (HSP) improved the diminished uptake capacity by 50% in comparison to the high sodium group. In conclusion, a high dietary content of sodium further enhances sympathetic activity and vascular reactivity in spSHR. This can be ascribed, in part, to a reduction of neuronal uptake of NA, with is restored to normal by partial replacement of sodium by potassium in the diet.
ECHOCARDIOGRAPHIC EVIDENCE FOR EARLY LEFT VENTRICULAR HYPERTROPHY IN RENAL HYPERTENSIVE DOGS Shigefumi Morioka, MD; Geza Simon, MD, Department of Medicine. University of Minnesota and V.A. Medical Center Minneapoiis, MN. . To investigate the rate of development of LV hypertrophy, LV wall thickness was measured with M-mode echocardiography in 10 awake male dogs for several weeks before (control) and for 6 weeks after the induction of hypertension. Hypertension was produced by wrapping (Wx) one kidney in silk followed 2 weeks later by contralateral nephrectomy (Nx). Echocardiographic measurements were performed 2 to 3 times weekly and were averaged. Three dogs with sham-Wx and contralateral Nx served as controls. Results (mean+SE) in hypertensive dogs were: Control Wx 1 Wx 2 Nx 2 Nx3-4 Nx5-6 Weeks Nx 1 141* 173*** 185*** 185*** 184** 125 138 (Zg) ;; +7 +4 +5 +9 + 13 + 15 gTg*xx 9.5x** 9.9*** 10.4***iO.8*** WTd . 8.2 +0.2 + 0.3 -44 44 44 +1.4 +1.3 + 1.5 (% MAP is mean arterial p&sure;
(mm)
5.2
+ 0.3 + 0.4 + 0.3 + 0.4 44 44 43** 43* +1.3 +1.6 + 1.6 21.2 Dd and Wfd are enddiastolic
LV dimension and LV wall thickness; *p
Volume 47
WEDNESDAY, MARCH 18, 1981 PM hfYPERTENS/ON-RESEARCH 4:OQ-5:oo
SYMPATHETIC ACTIVITY IN spSHR. Albert Schdmig, MD, Rainer Diets, MD, Wolfgang, Rascher,MD Ruth Strasser, MD, and Wolfgang Kiibler, MD, Dept. of Cardiology University of Heidelberg, Germany.
AGE-DEPENDENT ENHANCEMENT OF VASCULAR PHOSPHOLIPID (PL) DRACYLATION-RRACYLATION CYCLE IN SPONTANEOUSLY HYPERTEN~IVE RATS (SHRS). Catherine Limas,MD and Constantinos J.Limas,MD;Veterans Administration Medical Center and the University of Minnesota, Minneapolis, Minnesota. Substrate availability is a key step in prostaglandin (PG) synthesis regulation and depends,to a large extent,on the activity of membrane phospholipase A2(PLase). We havecompared PG synthesis and Plase activity inaortas of SHRs and WKYs as a function of age.At 7 weeks,there is no difference in either PG or Plase between the two groups.With advancing age,aortic PG synthesis increases in both SHRs and WKYs but is significantly higher in hypertensive rats (0.52*0.04 nmol PGI2/mg/l5 min in SHRs at 42 wks compared to 0.29+0.04 nmol/mg/l5 min in WKYs,p
AN EXPERIMEN~L MODEL To ~EI+IDNsTRATROBJECTIVELY ME AsSOCIATION OF LABILE HYPERTENSION TU VASCULAR COMPLICATION &&d A. -M.D.; Robert Barndt, M.D., University of Southern Calftornls, Los Angeles, CA. The association between labile hypertension and vascular complications has been suspected epldemlologically. In the absence of an objective method of validation, we deslgned a prospective, randomiced study to investigate Ztrenty-four New Zealand rabbits this quantitatively. were randomlsed into three equal groups. One group of 8 Two other rabblts were used as age-matched controls. groups were fed a high (2%) cholesterol (Chol.) diet for One group of Chol. fed rabbits was given ran6 months. dom numbers of noreplnephrine (NOR) infusions (1 mg per 30 minutes) dally during the fourth month of Chol. feeding to induce labile hypertension. Significant elevatlon of blood pressure (BP) compared to baseline BP was obtained (mea-172, range-140-190mm Hg, P
478
February 1981
The American Journal of CARDIOLOGY
Dietary sodium loading in stroke prone spontaneously hyper tensive rats (spSHR) accelerates the rise in blood pressure whereas a potassium rich diet causes an attenuation of the development of hypertension. Since sympathetic activity and vascular reactivity to noradrenaline (NA) is elevated in spSHR as compared to WKR, we investigated the effects of changes in dietary sodium and potassium content on these parameters. The reactivity of vascular smooth muscle to NA was enhanced following dietary sodium loading as compared to normal fed animals and rats on a diet in which sodium was partially replaced by potassium (HSP diet : 650 mm01 N&l/kg and 200 mm01 KCl/kg). A high sodium diet (HS diet: 1000 mm01 N&l/kg) for a period of 14 days resulted in a rise of plasma NA concentration after cold exposition from 368 + 53 to 842 + 30 rig/l and of adrenaline (A) from 245 + 71to 1168 + 357 rig/l,,being markedly less pronounced in normal fed-spSHR NA from 244 + 30 to 448 + 51 ng/ml and A from 202 + 56 to 374 + 49 ns/l. 1n addition, a supersensitivity 07 vasculatur~ to NA was observed (ED50: 1.66 + 0.18 vs 2.4 + 0.26 nmol NA), which was the consequence of a reduced cocaine dependent uptake (uptake 1) of NA after a high sodium diet (70 + 3 vs 96 + 8 pmol/min/g tissue). Feeding with the potassium substituted diet (HSP) improved the diminished uptake capacity by 50% in comparison to the high sodium group. In conclusion, a high dietary content of sodium further enhances sympathetic activity and vascular reactivity in spSHR. This can be ascribed, in part, to a reduction of neuronal uptake of NA, with is restored to normal by partial replacement of sodium by potassium in the diet.
ECHOCARDIOGRAPHIC EVIDENCE FOR EARLY LEFT VENTRICULAR HYPERTROPHY IN RENAL HYPERTENSIVE DOGS Shigefumi Morioka, MD; Geza Simon, MD, Department of Medicine. University of Minnesota and V.A. Medical Center Minneapoiis, MN. . To investigate the rate of development of LV hypertrophy, LV wall thickness was measured with M-mode echocardiography in 10 awake male dogs for several weeks before (control) and for 6 weeks after the induction of hypertension. Hypertension was produced by wrapping (Wx) one kidney in silk followed 2 weeks later by contralateral nephrectomy (Nx). Echocardiographic measurements were performed 2 to 3 times weekly and were averaged. Three dogs with sham-Wx and contralateral Nx served as controls. Results (mean+SE) in hypertensive dogs were: Control Wx 1 Wx 2 Nx 2 Nx3-4 Nx5-6 Weeks Nx 1 141* 173*** 185*** 185*** 184** 125 138 (Zg) ;; +7 +4 +5 +9 + 13 + 15 gTg*xx 9.5x** 9.9*** 10.4***iO.8*** WTd . 8.2 +0.2 + 0.3 -44 44 44 +1.4 +1.3 + 1.5 (% MAP is mean arterial p&sure;
(mm)
5.2
+ 0.3 + 0.4 + 0.3 + 0.4 44 44 43** 43* +1.3 +1.6 + 1.6 21.2 Dd and Wfd are enddiastolic
LV dimension and LV wall thickness; *p
Volume 47