PMID- 37823205
OWN - NLM
STAT- MEDLINE
DCOM- 20231121
LR  - 20240314
IS  - 1522-1601 (Electronic)
IS  - 0161-7567 (Linking)
VI  - 135
IP  - 6
DP  - 2023 Dec 1
TI  - Angiotensin II type 2 receptor-mediated dilation is greater in the cutaneous 
      microvasculature of premenopausal women compared with men.
PG  - 1236-1242
LID - 10.1152/japplphysiol.00382.2023 [doi]
AB  - Differential activation of the renin-angiotensin system (RAS) likely contributes 
      to sex differences in cardiovascular outcomes in premenopausal women compared 
      with age-matched men. Women demonstrate reduced activation of the vasoconstrictor 
      angiotensin II type 1 receptors (AT(1)R) compared with men, and evidence suggests 
      that women also likely have increased sensitivity of the vasodilatory angiotensin 
      II type 2 receptors (AT(2)R). However, few in vivo studies have directly examined 
      sex differences in AT(2)R-mediated dilation, or the balance between AT(1)R- and 
      AT(2)R-mediated vascular responses in humans. Using the cutaneous 
      microcirculation as a model, we hypothesized that AT(2)R-mediated dilation would 
      be greater in premenopausal women compared with men, and that AT(1)R-blockade 
      would augment AT(2)R-mediated dilation to a greater extent in men than in women. 
      Twelve healthy women (22 +/- 3 yr) and 12 men (23 +/- 5 yr) had two intradermal 
      microdialysis fibers placed in the ventral forearm for graded infusions of 
      compound 21 (AT(2)R agonist; 10(-12) to 10(-8) M) in a control fiber site and a 
      site treated with 43 microM losartan (AT(1)R antagonist). Red blood cell flux was 
      measured continuously by laser-Doppler flowmetry, and cutaneous vascular 
      conductance [CVC = flux/mean arterial pressure (MAP)] was normalized to maximum 
      [%max; 28 mM sodium nitroprusside (SNP) + 43  degrees C]. Women had greater 
      AT(2)R-mediated dilation compared with men (women: 25 +/- 4 vs. men: 15 +/- 2%max, P 
      = 0.03). Local AT(1)R inhibition increased AT(2)R-mediated dilation in men 
      (losartan: 26 +/- 4 vs. control: 15 +/- 2%max, P < 0.001) but had no effect in women 
      (losartan: 27 +/- 6 vs. control: 25 +/- 4%max, P > 0.05). These data suggest that 
      premenopausal women have a greater AT(2)R-mediated vasodilation response than 
      men, and that AT(1)R activation inhibits AT(2)R-mediated dilation in men, but not 
      in women.NEW & NOTEWORTHY Premenopausal women have greater protection against 
      cardiovascular disease than age-matched men. However, the role of vasoconstrictor 
      angiotensin II type 1 receptors (AT(1)R) and vasodilatory angiotensin II type 2 
      receptors (AT(2)R) in mediating these sex differences is unclear. Here, we 
      demonstrate that women have greater AT(2)R-mediated vasodilation than men and 
      that AT(1)R negates AT(2)R-mediated dilation in men, but not in women.
FAU - Schwartz, Kelsey S
AU  - Schwartz KS
AUID- ORCID: 0000-0002-1418-1813
AD  - Department of Health and Human Physiology, The University of Iowa, Iowa City, 
      Iowa, United States.
FAU - Lang, James A
AU  - Lang JA
AUID- ORCID: 0000-0002-5179-1434
AD  - Department of Kinesiology, Iowa State University, Ames, Iowa, United States.
FAU - Stanhewicz, Anna E
AU  - Stanhewicz AE
AUID- ORCID: 0000-0002-3941-3879
AD  - Department of Health and Human Physiology, The University of Iowa, Iowa City, 
      Iowa, United States.
LA  - eng
GR  - HL-138133-05/HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20231012
PL  - United States
TA  - J Appl Physiol (1985)
JT  - Journal of applied physiology (Bethesda, Md. : 1985)
JID - 8502536
RN  - 0 (Receptor, Angiotensin, Type 2)
RN  - JMS50MPO89 (Losartan)
RN  - 11128-99-7 (Angiotensin II)
RN  - 0 (Vasoconstrictor Agents)
SB  - IM
EIN - J Appl Physiol (1985). 2024 Feb 1;136(2):399. PMID: 38324362
MH  - Humans
MH  - Female
MH  - Male
MH  - *Receptor, Angiotensin, Type 2
MH  - *Losartan/pharmacology
MH  - Angiotensin II
MH  - Dilatation
MH  - Microvessels
MH  - Vasoconstrictor Agents
OTO - NOTNLM
OT  - angiotensin II
OT  - microvasculature
OT  - sex differences
OT  - vasodilation
EDAT- 2023/10/12 06:43
MHDA- 2023/11/21 06:43
CRDT- 2023/10/12 04:22
PHST- 2023/11/21 06:43 [medline]
PHST- 2023/10/12 06:43 [pubmed]
PHST- 2023/10/12 04:22 [entrez]
AID - 10.1152/japplphysiol.00382.2023 [doi]
PST - ppublish
SO  - J Appl Physiol (1985). 2023 Dec 1;135(6):1236-1242. doi: 
      10.1152/japplphysiol.00382.2023. Epub 2023 Oct 12.